Journal articles: 'Post-Translational Protein Processing'

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Johnson, Amy L., Paola Braidotti, Giuseppe G. Pietra, Scott J. Russo, Albert Kabore, Wen-Jing Wang, and Michael F. Beers. "Post-Translational Processing of Surfactant Protein-C Proprotein." American Journal of Respiratory Cell and Molecular Biology 24, no. 3 (March 2001): 253–63. http://dx.doi.org/10.1165/ajrcmb.24.3.4312.

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Zencheck, Wendy D., Hui Xiao, and Louis M. Weiss. "Lysine post-translational modifications and the cytoskeleton." Essays in Biochemistry 52 (May 25, 2012): 135–45. http://dx.doi.org/10.1042/bse0520135.

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PTMs (post-translational modifications) of lysine residues have proven to be major regulators of gene expression, protein–protein interactions, and protein processing and degradation. This is of particular importance in regulating the cytoskeleton, an enormously complex system of proteins responsible for cell motility, intracellular trafficking, and maintenance of cell form and structure. The cytoskeleton is present in all cells, including eukaryotes and prokaryotes, and comprises structures such as flagella, cilia and lamellipodia which play critical roles in intracellular transport and cellular division. Cytoskeletal regulation relies on numerous multi-component assemblies. In this chapter, we focus on the regulation of the cytoskeleton by means of PTMs of lysine residues on the cytoskeletal subunits and their accessory proteins. We specifically address the three main classes of cytoskeletal proteins in eukaryotes that polymerize into filaments, including microfilaments (actin filaments), intermediate filaments and microtubules. We discuss the identification and biological importance of lysine acetylation, a regulator of all three filament types. We also review additional lysine modifications, such as ubiquitination and SUMOylation, and their role in protein regulation and processing.

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Tacchi, Jessica L., Benjamin B. A. Raymond, Paul A. Haynes, Iain J. Berry, Michael Widjaja, Daniel R. Bogema, Lauren K. Woolley, et al. "Post-translational processing targets functionally diverse proteins in Mycoplasma hyopneumoniae." Open Biology 6, no. 2 (February 2016): 150210. http://dx.doi.org/10.1098/rsob.150210.

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Mycoplasma hyopneumoniae is a genome-reduced, cell wall-less, bacterial pathogen with a predicted coding capacity of less than 700 proteins and is one of the smallest self-replicating pathogens. The cell surface of M. hyopneumoniae is extensively modified by processing events that target the P97 and P102 adhesin families. Here, we present analyses of the proteome of M. hyopneumoniae- type strain J using protein-centric approaches (one- and two-dimensional GeLC–MS/MS) that enabled us to focus on global processing events in this species. While these approaches only identified 52% of the predicted proteome (347 proteins), our analyses identified 35 surface-associated proteins with widely divergent functions that were targets of unusual endoproteolytic processing events, including cell adhesins, lipoproteins and proteins with canonical functions in the cytosol that moonlight on the cell surface. Affinity chromatography assays that separately used heparin, fibronectin, actin and host epithelial cell surface proteins as bait recovered cleavage products derived from these processed proteins, suggesting these fragments interact directly with the bait proteins and display previously unrecognized adhesive functions. We hypothesize that protein processing is underestimated as a post-translational modification in genome-reduced bacteria and prokaryotes more broadly, and represents an important mechanism for creating cell surface protein diversity.

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O. Solarin, Wen-Jing Wang, Michael, Kolawole. "SYNTHESIS AND POST-TRANSLATIONAL PROCESSING OF SURFACTANT PROTEIN C." Pediatric Pathology & Molecular Medicine 20, no. 6 (November 1, 2001): 471–500. http://dx.doi.org/10.1080/15227950152625792.

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O. Solarin, Wen-Jing Wang, Michael, Kolawole. "SYNTHESIS AND POST-TRANSLATIONAL PROCESSING OF SURFACTANT PROTEIN C." Pediatric Pathology & Molecular Medicine 20, no. 6 (January 2001): 471–500. http://dx.doi.org/10.1080/pdp.20.6.471.500.

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Christensen, Brian, Torben E. Petersen, and Esben S. Sørensen. "Post-translational modification and proteolytic processing of urinary osteopontin." Biochemical Journal 411, no. 1 (March 13, 2008): 53–61. http://dx.doi.org/10.1042/bj20071021.

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OPN (osteopontin) is a highly phosphorylated glycoprotein present in many tissues and body fluids. In urine, OPN is a potent inhibitor of nucleation, growth and aggregation of calcium oxalate crystals, suggesting that it has a role in the prevention of renal stone formation. The role of OPN in nephrolithiasis is, however, somewhat unclear, as it may also be involved in urinary stone formation, and it has been identified among the major protein components of renal calculi. Most likely, the function of OPN in urine is dependent on the highly anionic character of the protein. Besides a very high content of aspartic and glutamic residues, OPN is subjected to significant PTM (post-translational modification), such as phosphorylation, sulfation and glycosylation, which may function as regulatory switches in promotion or inhibition of mineralization. In the present study, we have characterized the PTMs of intact human urinary OPN and N-terminal fragments thereof. MS analysis showed a mass of 37.7 kDa for the intact protein. Enzymatic dephosphorylation and peptide mass analyses demonstrated that the protein contains approximately eight phosphate groups distributed over 30 potential phosphorylation sites. In addition, one sulfated tyrosine and five O-linked glycosylations were identified in OPN, whereas no N-linked glycans were detected. Peptide mapping and immunoblotting using different monoclonal antibodies showed that the N-terminal fragments present in urine are generated by proteolytic cleavage at Arg228–Leu229 and Tyr230–Lys231.

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Verschoor, Ernst J., Ellen G. J. Hulskotte, Joke Ederveen, Marck J. M. Koolen, Marian O. Horzinek, and Peter J. M. Rottier. "Post-translational Processing of the Feline Immunodeficiency Virus Envelope Precursor Protein." Virology 193, no. 1 (March 1993): 433–38. http://dx.doi.org/10.1006/viro.1993.1140.

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Georgopoulou, Niki, Mark McLaughlin, Ian McFarlane, and Kieran C. Breen. "The role of post-translational modification in ϐ-amyloid precursor protein processing." Biochemical Society Symposia 67 (February 1, 2001): 23–36. http://dx.doi.org/10.1042/bss0670023.

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The ϐ-amyloid precursor protein (APP) plays a pivotal role in the early stages of neurodegeneration associated with Alzheimer's disease. An alteration in the processing pattern of the protein results in an increase in the generation of the 40-42-amino-acid ϐ-amyloid (Aϐ) peptide, which coalesces to form insoluble, extracellular amyloid deposits. A greater understanding of the factors that influence APP processing may assist in the design of effective therapeutic agents to halt progression of Alzheimer's disease. APP is a sialoglycoprotein with two potential N-linked glycosylation sites, one of which may contain a complex oligosaccharide chain. An alteration in the glycosylation state of APP by the generation of oligomannosyl oligosaccharides results in a decrease in the secretion of the neuroprotective, soluble form of the protein and a parallel increase in the deposition of the cellular protein within the perinuclear region of the cell. Conversely, the attachment of additional terminal sialic acid residues on to the oligosaccharide chain results in an increase in secretion of soluble APP (sAPPα). One factor that has been widely reported to alter APP processing is the activation of protein kinase C (PKC). This process has been characterized using synaptosomal preparations, which suggests that the PKC action is occurring at the level of the plasma membrane. Furthermore, when cells are transfected with the sialyltransferase enzyme, there is a direct relationship between the sialylation potential of APP and the fold stimulation of sAPPα, after PKC activation. These results suggest that the post-translational modification of APP by glycosylation is a key event in determining the processing of the protein.

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Snijder, Eric J., Johan A. Den Boon, Willy J. M. Spaan, Marianne Weiss, and Marian C. Horzinek. "Primary structure and post-translational processing of the berne virus peplomer protein." Virology 178, no. 2 (October 1990): 355–63. http://dx.doi.org/10.1016/0042-6822(90)90332-l.

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Qin, C., O. Baba, and W. T. Butler. "Post-translational Modifications of SIBLING Proteins and Their Roles in Osteogenesis and Dentinogenesis." Critical Reviews in Oral Biology & Medicine 15, no. 3 (May 2004): 126–36. http://dx.doi.org/10.1177/154411130401500302.

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The extracellular matrix (ECM) of bone and dentin contains several non-collagenous proteins. One category of non-collagenous protein is termed the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family, that includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE). These polyanionic SIBLING proteins are believed to play key biological roles in the mineralization of bone and dentin. Although the specific mechanisms involved in controlling bone and dentin formation are still unknown, it is clear that some functions of the SIBLING family members are dependent on the nature and extent of post-translational modifications (PTMs), such as phosphorylation, glycosylation, and proteolytic processing, since these PTMs would have significant effects on their structure. OPN and BSP are present in the ECM of bone and dentin as full-length forms, whereas amino acid sequencing indicates that DMP1 and DSPP exist as proteolytically processed fragments that result from scission of X-Asp bonds. We hypothesized that the processing of DMP1 and DSPP is catalyzed by the PHEX enzyme, since this protein, an endopeptidase that is predominantly expressed in bone and tooth, has a strong preference for cleavage at the NH2-terminus of aspartyl residue. We envision that the proteolytic processing of DMP1 and DSPP may be an activation process that plays a significant, crucial role in osteogenesis and dentinogenesis, and that a failure in this processing would cause defective mineralization in bone and dentin, as observed in X-linked hypophosphatemic rickets.

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Mikuni-Takagaki, Y., and M. J. Glimcher. "Post-translational processing of chicken bone phosphoproteins. Identification of bone (phospho)protein kinase." Biochemical Journal 268, no. 3 (June 15, 1990): 593–97. http://dx.doi.org/10.1042/bj2680593.

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We have detected a protein kinase which phosphorylates bone phosphoproteins (BPPs) in the detergent extract of the membranous fractions in the periosteal bone strips of 12-day-embryonic-chick tibia. This enzyme, tentatively named BPP kinase, has a catalytic subunit of Mr approximately 39,000, utilizes GTP as well as ATP as a phospho-group donor, is inhibited by 2,3-bisphosphoglycerate and heparin, and is therefore similar to casein kinase II. The enzyme can phosphorylate dephosphorylated proteins such as casein, phosvitin and chicken BPPs, but the last-named are preferred substrates. The in vitro-phosphorylation-assay products of this enzyme in the extract were indistinguishable on an SDS/polyacrylamide gel from the major [32P]phosphoproteins metabolically labelled in the embryonic-chick bone tissue. The regulatory mechanisms of the phosphorylation process of BPPs by BPP kinase as well as the potential role of this enzyme in mineralization are discussed.

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Kermode, Allison R. "Plants as factories for production of biopharmaceutical and bioindustrial proteins: lessons from cell biologyThis review is one of a selection of papers published in the Special Issue on Plant Cell Biology." Canadian Journal of Botany 84, no. 4 (April 2006): 679–94. http://dx.doi.org/10.1139/b06-069.

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Transgenic plants, seeds, and cultured plant cells are potentially one of the most economical systems for large-scale production of recombinant proteins for industrial and pharmaceutical uses. Biochemical, technical, and economic concerns with current production systems have generated enormous interest in developing plants as alternative production systems. However, various challenges must be met before plant systems can fully emerge as suitable, viable alternatives to current animal-based systems for large-scale production of biopharmaceuticals and other products. Aside from regulatory issues and developing efficient methods for downstream processing of recombinant proteins, there are at least two areas of challenge: (1) Can we engineer plant cells to accumulate recombinant proteins to sufficient levels? (2) Can we engineer plant cells to post-translationally modify recombinant proteins so that they are structurally and functionally similar to the native proteins? Attempts to improve the accumulation of a recombinant protein in plant cells require an appreciation of the processes of gene transcription, mRNA stability, processing, and export, and translation initiation and efficiency. Likewise, many post-translational factors must be considered, including protein stability, protein function and activity, and protein targeting. Moreover, we need to understand how the various processes leading from the gene to the functional protein are interdependent and functionally linked. Manipulation of the post-translational processing machinery of plant cells, especially that for N-linked glycosylation and glycan processing, is a challenging and exciting area. The functions of N-glycan heterogeneity and microheterogeneity, especially with respect to protein function, stability, and transport, are poorly understood and this represents an important area of cell biology.

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Orlova, N. A., S. V. Kovnir, I. I. Vorobiev, A. G. Gabibov, and A. I. Vorobiev. "Blood Clotting Factor VIII: From Evolution to Therapy." Acta Naturae 5, no. 2 (June 15, 2013): 19–39. http://dx.doi.org/10.32607/20758251-2013-5-2-19-39.

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Recombinant blood clotting factor VIII is one of the most complex proteins for industrial manufacturing due to the low efficiency of its gene transcription, massive intracellular loss of its proprotein during post-translational processing, and the instability of the secreted protein. Improvement in hemophilia A therapy requires a steady increase in the production of factor VIII drugs despite tightening standards of product quality and viral safety. More efficient systems for heterologous expression of factor VIII can be created on the basis of the discovered properties of its gene transcription, post-translational processing, and behavior in the bloodstream. The present review describes the deletion variants of factor VIII protein with increased secretion efficiency and the prospects for the pharmaceutical development of longer acting variants and derivatives of factor VIII.

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Han, Jianzhong, and Ellen Townes-Anderson. "Cell Specific Post-Translational Processing of Pikachurin, A Protein Involved in Retinal Synaptogenesis." PLoS ONE 7, no. 12 (December 4, 2012): e50552. http://dx.doi.org/10.1371/journal.pone.0050552.

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Giannakouros, T., C. M. Newman, M. W. Craighead, J. Armstrong, and A. I. Magee. "Post-translational processing of Schizosaccharomyces pombe YPT5 protein. In vitro and in vivo analysis of processing mutants." Journal of Biological Chemistry 268, no. 32 (November 1993): 24467–74. http://dx.doi.org/10.1016/s0021-9258(20)80549-3.

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Rhee, David K., Jose Marcelino, Sulaiman Al-Mayouf, Deborah K. Schelling, Cynthia F. Bartels, Yajun Cui, Ronald Laxer, Raphaela Goldbach-Mansky, and Matthew L. Warman. "Consequences of Disease-causing Mutations on Lubricin Protein Synthesis, Secretion, and Post-translational Processing." Journal of Biological Chemistry 280, no. 35 (July 5, 2005): 31325–32. http://dx.doi.org/10.1074/jbc.m505401200.

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Maurer, Christian, Hsiu-Cheng Hung, and Frank Weber. "Cytoplasmic interaction with CYCLE promotes the post-translational processing of the circadian CLOCK protein." FEBS Letters 583, no. 10 (April 17, 2009): 1561–66. http://dx.doi.org/10.1016/j.febslet.2009.04.013.

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O'Reilly, Michael A., Timothy E. Weaver, Tami J. Pilot-Matias, Virender K. Sarin, Adi F. Gazdar, and Jeffrey A. Whitsett. "In vitro translation, post-translational processing and secretion of pulmonary surfactant protein B precursors." Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1011, no. 2-3 (May 1989): 140–48. http://dx.doi.org/10.1016/0167-4889(89)90201-2.

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KUGE, Osamu, Kyoko SAITO, Michiyuki KOJIMA, Yuzuru AKAMATSU, and Masahiro NISHIJIMA. "Post-translational processing of the phosphatidylserine decarboxylase gene product in Chinese hamster ovary cells." Biochemical Journal 319, no. 1 (October 1, 1996): 33–38. http://dx.doi.org/10.1042/bj3190033.

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We have isolated a full-length cDNA clone of the Chinese hamster ovary (CHO) pssC gene, which encodes mitochondrial phosphatidylserine decarboxylase. The cDNA clone is capable of increasing phosphatidylserine decarboxylase activity to 11-fold in CHO-K1 cells. The pssC gene product predicted from the cDNA sequence is composed of 409 amino acid residues. In an in vitro translation system coupled with in vitro transcription, the cDNA clone directs the formation of a protein with an apparent molecular mass of 46 kDa. In CHO-K1 cells, the cDNA clone leads to the production of two major peptides with apparent molecular masses of 38 and 34 kDa, as determined by Western blotting with an antibody raised against a recombinant pssC protein. When CHO-K1 cells transfected with the cDNA clone are labelled with [35S]methionine for a short period, proteins immunoprecipitated with the antibody lack radioactive 38 and 34 kDa peptides, but contain two radioactive peptides with apparent molecular masses of 46 and 42 kDa instead. The pssC gene product predicted from the cDNA sequence has, near its C-terminus, a unique Leu-Gly-Ser-Thr sequence which is known as a processing site for Escherichia coli phosphatidylserine decarboxylase. A mutant pssC cDNA clone, in which Ser378 in the conserved sequence is replaced by Ala, leads to overproduction of 46, 42 and 38 kDa peptides, but not a 34 kDa peptide. This mutant clone is incapable of increasing phosphatidylserine decarboxylase activity, in contrast to the wild-type clone. These results indicate that the processing at the Leu-Gly-Ser-Thr sequence is essential for formation of the active enzyme. Thus, the pssC gene product is converted into mature phosphatidylserine decarboxylase through multiple steps of post-translational processing.

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Mikuni-Takagaki, Y., and M. J. Glimcher. "Post-translational processing of chicken bone phosphoproteins. Identification of the bone phosphoproteins of embryonic tibia." Biochemical Journal 268, no. 3 (June 15, 1990): 585–91. http://dx.doi.org/10.1042/bj2680585.

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In order to understand the mechanism of the post-translational processing of bone phosphoproteins in embryonic bone, periosteal bone strips isolated from 12-day-embryonic-chick tibiae were cultured and the bone proteins labelled with Na2H32PO4. Of the total radiolabelled proteins recovered from the medium and bone extracts in the absence of SDS (‘medium’, ‘EDTA extract’ and ‘EDTA/guanidinium chloride extract’), nearly 80% of the radioactivity was found in the EDTA extract. The three major radiolabelled phosphoproteins in the EDTA extract of apparent Mr 68,000, 63,000 and 58,000 reacted with polyclonal as well as monoclonal antibodies raised against ‘32-kDa’ and ‘150-kDa’ bone phosphoproteins which were derived from 14-week-old chicken. Therefore these phosphorylated embryonic proteins are identified as chicken bone phosphoproteins. Judging from their common N-terminal sequences, differences in the patterns obtained by labelling them with several radioisotopes, and slightly different amino acid compositions, these components seem to have been derived from the same original protein by sequential proteolytic cleavage and other processing such as glycosylation and phosphorylation.

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Hanada, Ken-ichi, and James C. Yang. "Novel biochemistry: post-translational protein splicing and other lessons from the school of antigen processing." Journal of Molecular Medicine 83, no. 6 (March 10, 2005): 420–28. http://dx.doi.org/10.1007/s00109-005-0652-6.

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Sato, Yukihiro, and Okitsugu Yamashita. "Post-translational processing in the synthesis of egg-specific protein in the silkworm, Bombyx mori." Insect Biochemistry 19, no. 3 (January 1989): 293–300. http://dx.doi.org/10.1016/0020-1790(89)90075-9.

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Hinrichsen, M., M. Lenz, J. M. Edwards, O. K. Miller, S. G. J. Mochrie, P. S. Swain, U. Schwarz-Linek, and L. Regan. "A new method for post-translationally labeling proteins in live cells for fluorescence imaging and tracking." Protein Engineering, Design and Selection 30, no. 12 (December 1, 2017): 771–80. http://dx.doi.org/10.1093/protein/gzx059.

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AbstractWe present a novel method to fluorescently label proteins, post-translationally, within live Saccharomycescerevisiae. The premise underlying this work is that fluorescent protein (FP) tags are less disruptive to normal processing and function when they are attached post-translationally, because target proteins are allowed to fold properly and reach their final subcellular location before being labeled. We accomplish this post-translational labeling by expressing the target protein fused to a short peptide tag (SpyTag), which is then covalently labeled in situ by controlled expression of an open isopeptide domain (SpyoIPD, a more stable derivative of the SpyCatcher protein) fused to an FP. The formation of a covalent bond between SpyTag and SpyoIPD attaches the FP to the target protein. We demonstrate the general applicability of this strategy by labeling several yeast proteins. Importantly, we show that labeling the membrane protein Pma1 in this manner avoids the mislocalization and growth impairment that occur when Pma1 is genetically fused to an FP. We also demonstrate that this strategy enables a novel approach to spatiotemporal tracking in single cells and we develop a Bayesian analysis to determine the protein’s turnover time from such data.

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Héron, A., J. Bourguignon, A. Callé, H. Borghi, R. Sesboüé, M. Diarra-Mehrpour, and J. P. Martin. "Post-translational processing of the inter-α-trypsin inhibitor in the human hepatoma HepG2 cell line." Biochemical Journal 302, no. 2 (September 1, 1994): 573–80. http://dx.doi.org/10.1042/bj3020573.

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In human hepatoma HepG2 cells, the serum inter-alpha-trypsin inhibitor (ITI)-like protein is synthesized from two protein precursors, the heavy chain (H) H2 and the light chain (L). Both of them carry sulphate groups involved in the chondroitin sulphate glycosaminoglycan (GAG) linkage, as demonstrated by [35S]sulphate labelling, chondroitinase digestion and inhibition with beta-D-xyloside, an artificial GAG acceptor. While inhibition of N-glycosylation prevented neither the maturation nor the secretion of the ITI-related entities, brefeldin A induced the accumulation of H and L precursors in the cells, therefore blocking subsequent association and maturation of the precursors before their secretion. The enzyme system involved in the ester linkage between H and L chains is localized in the trans-Golgi network since no ITI-like protein could be obtained in the presence of monensin; instead free heavy-chain protein forms and bikunin were secreted in culture supernatants. The ITI-like protein synthesized by HepG2 cells is therefore composed of two heavy chains HC2 linked to two bikunin chains by chondroitin sulphate bridges, although the GAG linkage between HC2 chains is presumably different. Further, a different maturation route leading to restricted heavy-chain forms, Hm and Hd, could be shown.

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Campa, M. J., F. X. Farrell, E. G. Lapetina, and K. J. Chang. "Microinjection of Rap2B protein or RNA induces rearrangement of pigment granules in Xenopus oocytes." Biochemical Journal 292, no. 1 (May 15, 1993): 231–36. http://dx.doi.org/10.1042/bj2920231.

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Rap2B, a member of the ras superfamily of low-molecular-mass GTP-binding proteins, induced a characteristic rearrangement of the pigment granules in Xenopus oocytes following its microinjection, resulting in numerous unpigmented spots on the animal hemisphere. This phenomenon, termed ‘mottling‘, was also induced by microinjection of in vitro-transcribed Rap2B RNA or of purified recombinant Rap2A. Following the microinjection of Rap2B, more than 90% of the oocytes showed signs of mottling within 10 h. The time course of mottling paralleled the association of the recombinant Rap2B with an oocyte membrane fraction. Like other members of the ras superfamily, Rap2B possesses a C-terminal CAAX motif that serves as a signal for post-translational processing. Mutation of the cysteine residue in the CAAX motif to serine prevents the association of Rap2B with oocyte membranes, and also prevents mottling. This result suggests that post-translational processing of Rap2B is required for the observed effect. Mottling was blocked by boiling Rap2B prior to its microinjection or by co-injection of the cytoskeletal reagent phalloidin.

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Yao, Shixiang, and Chibuike C. Udenigwe. "Peptidomics of potato protein hydrolysates: implications of post-translational modifications in food peptide structure and behaviour." Royal Society Open Science 5, no. 7 (July 2018): 172425. http://dx.doi.org/10.1098/rsos.172425.

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Post-translational modifications (PTMs) often occur in proteins and play a regulatory role in protein function. There is an increasing interest in the bioactivity of food protein-derived peptides, but the occurrence of PTMs and their influence on food peptide structure and behaviour remain largely unknown. In this study, the shotgun-based peptidomics strategy was used to identify the occurrence of PTMs in peptides generated from potato protein hydrolysis using digestive proteases. Diverse PTMs were found in the potato peptides, including acetylation of lysine, N-terminal of proteins and peptides, C-terminal amidation, de-amidation of asparagine/glutamine, methylation and trimethylation, methionine oxidation and N-terminal pyro-glutamyl residue formation. The modifications may have been formed naturally or as a result of chemical reactions during isolation and enzymatic processing of the potato proteins. Most of the PTMs were calculated to decrease the isoelectric point and increase molecular hydrophobicity of the peptides, which will influence their bioactivity while also potentially altering their solubility in an aqueous environment. This is the first study to unravel that food-derived peptides can be widely modified by PTMs associated with notable changes in peptide chemical properties. The findings have broader implications on the bioavailability, biomolecular interactions and biological activities of food peptides.

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Panigrahi*, Gagan Kumar, Annapurna Sahoo, and Sasmita Panda. "A complex network of molecular events triggered upon environmental cues which decide the fate of gene expression: a review." International Journal of Bioassays 5, no. 12 (December 4, 2016): 5185. http://dx.doi.org/10.21746/ijbio.2016.12.0013.

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Gene expression in eukaryotes depends on a web of events which are inter-related and tightly regulated. These key events can be broadly classified into post-transcriptional and post-translational processes. In general, the post-transcriptional events include pre-mRNA processing (capping, splicing, polyadenylation), RNA stability, and translation as well as chromatin modifications through regulatory RNAs (miRNA, siRNAs and long non-coding RNAs). Protein phosphorylation, ubiquitination and sumoylation are a few post-translational events. These events are constitutive as well as provoked by specific exogenous and/or endogenous stimuli. In case of the plant system, the molecular mechanisms responsible for regulating the gene expression is diverse and yet to be fully revealed. The network of post-transcriptional and post-translational events do ensure temporal and spatial suitable patterns of downstream stress-related gene expression. The current review mainly focus on a variety of molecular events which play a pivotal role in fine tuning the gene expression in eukaryotes.

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Romer, Terence G., and Michael D. P. Boyle. "Application of immunoproteomics to analysis of post-translational processing of the antiphagocytic M protein of Streptococcus." PROTEOMICS 3, no. 1 (January 2003): 29–35. http://dx.doi.org/10.1002/pmic.200390005.

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Afrin, Taiaba, Danish Diwan, Katrina Sahawneh, and Karolina Pajerowska-Mukhtar. "Multilevel regulation of endoplasmic reticulum stress responses in plants: where old roads and new paths meet." Journal of Experimental Botany 71, no. 5 (November 4, 2019): 1659–67. http://dx.doi.org/10.1093/jxb/erz487.

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Abstract The sessile lifestyle of plants requires them to cope with a multitude of stresses in situ. In response to diverse environmental and intracellular cues, plant cells respond by massive reprogramming of transcription and translation of stress response regulators, many of which rely on endoplasmic reticulum (ER) processing. This increased protein synthesis could exceed the capacity of precise protein quality control, leading to the accumulation of unfolded and/or misfolded proteins that triggers the unfolded protein response (UPR). Such cellular stress responses are multilayered and executed in different cellular compartments. Here, we will discuss the three main branches of UPR signaling in diverse eukaryotic systems, and describe various levels of ER stress response regulation that encompass transcriptional gene regulation by master transcription factors, post-transcriptional activities including cytoplasmic splicing, translational control, and multiple post-translational events such as peptide modifications and cleavage. In addition, we will discuss the roles of plant ER stress sensors in abiotic and biotic stress responses and speculate on the future prospects of engineering these signaling events for heightened stress tolerance.

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Martínez-Maldonado, Alejandra, Miguel Ángel Ontiveros-Torres, Charles R. Harrington, José Francisco Montiel-Sosa, Raúl García-Tapia Prandiz, Patricia Bocanegra-López, Andrew Michael Sorsby-Vargas, et al. "Molecular Processing of Tau Protein in Progressive Supranuclear Palsy: Neuronal and Glial Degeneration." Journal of Alzheimer's Disease 79, no. 4 (February 16, 2021): 1517–31. http://dx.doi.org/10.3233/jad-201139.

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Background: Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP) are examples of neurodegenerative diseases, characterized by abnormal tau inclusions, that are called tauopathies. AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. PSP is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with repeated microtubule-binding domains of three (3R) or four (4R) repeats. In AD, the 4R:3R ratio is 1:1. In PSP, the 4R isoform predominates. The lesions in PSP brains contain phosphorylated tau aggregates in both neurons and glial cells. Objective: Our objective was to evaluate and compare the processing of pathological tau in PSP and AD. Methods: Double and triple immunofluorescent labeling with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) staining were carried out and analyzed by confocal microscopy. Results: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Tau truncated at either Glu391 or Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR in the absence of intact or phosphorylated tau. Conclusion: Phosphorylated tau was as abundant in PSP as in AD. The development of eNFTs from both glial cells and neuronal bodies suggests that truncated tau species, different from those observed in AD, could be present in PSP. Additional studies on truncated tau within PSP lesions could improve our understanding of the pathological processing of tau and help identify a discriminatory biomarker for AD and PSP.

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Robishaw, J. D., V. K. Kalman, and K. L. Proulx. "Production, processing and partial purification of functional G protein βγ subunits in baculovirus-infected insect cells." Biochemical Journal 286, no. 3 (September 15, 1992): 677–80. http://dx.doi.org/10.1042/bj2860677.

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As a result of the inability to resolve the heterogeneous mixture of G protein beta gamma subunits present in tissues, it has not been possible to compare different beta gamma subunits of the G proteins in terms of their proposed roles in receptor-effector coupling. This study was undertaken to establish the utility of the baculovirus expression system in producing homogeneous beta gamma subunits of defined composition for the comparative analysis of these subunits in reconstitution systems. In this study we report the expression, and appropriate post-translational processing, of recombinant beta 2, gamma 2 and gamma 3 subunits. In addition, we show that the recombinant beta gamma subunits can be readily purified, and can functionally interact with the alpha subunits of the G proteins.

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Itoh, T., K. Kaibuchi, T. Masuda, T. Yamamoto, Y. Matsuura, A. Maeda, K. Shimizu, and Y. Takai. "The post-translational processing of ras p21 is critical for its stimulation of mitogen-activated protein kinase." Journal of Biological Chemistry 268, no. 5 (February 1993): 3025–28. http://dx.doi.org/10.1016/s0021-9258(18)53651-6.

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Behrens, Timothy W., Grainne M. Kearns, James J. Rivard, Harris D. Bernstein, Jonathan W. Yewdell, and Louis M. Staudt. "Carboxyl-terminal Targeting and Novel Post-translational Processing of JAW1, a Lymphoid Protein of the Endoplasmic Reticulum." Journal of Biological Chemistry 271, no. 38 (September 20, 1996): 23528–34. http://dx.doi.org/10.1074/jbc.271.38.23528.

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Papa, Sergio, Salvatore Scacco, Domenico De Rasmo, Anna Signorile, Francesco Papa, Damiano Panelli, Annarita Nicastro, et al. "cAMP-dependent protein kinase regulates post-translational processing and expression of complex I subunits in mammalian cells." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1797, no. 6-7 (June 2010): 649–58. http://dx.doi.org/10.1016/j.bbabio.2010.03.013.

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Zhu, Yi, and Gerald W. Hart. "Nutrient regulation of the flow of genetic information by O-GlcNAcylation." Biochemical Society Transactions 49, no. 2 (March 26, 2021): 867–80. http://dx.doi.org/10.1042/bst20200769.

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O-linked-β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (PTM) that is actively added to and removed from thousands of intracellular proteins. As a PTM, O-GlcNAcylation tunes the functions of a protein in various ways, such as enzymatic activity, transcriptional activity, subcellular localization, intermolecular interactions, and degradation. Its regulatory roles often interplay with the phosphorylation of the same protein. Governed by ‘the Central Dogma’, the flow of genetic information is central to all cellular activities. Many proteins regulating this flow are O-GlcNAc modified, and their functions are tuned by the cycling sugar. Herein, we review the regulatory roles of O-GlcNAcylation on the epigenome, in DNA replication and repair, in transcription and in RNA processing, in protein translation and in protein turnover.

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Burkhardt, J. K., and Y. Argon. "Intracellular transport of the glycoprotein of VSV is inhibited by CCCP at a late stage of post-translational processing." Journal of Cell Science 92, no. 4 (April 1, 1989): 633–42. http://dx.doi.org/10.1242/jcs.92.4.633.

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The appearance of newly synthesized glycoprotein (G) of vesicular stomatitis virus at the surface of infected BHK cells is inhibited reversibly by treatment with carbonylcyanide m-chlorophenylhydrazone (CCCP). Under the conditions used, CCCP treatment depleted the cellular ATP levels by 40–60%, consistent with inhibition of transport at energy-requiring stages. The G protein that accumulates in cells treated with CCCP is heterogeneous. Most of it is larger than the newly synthesized G protein, is acylated with palmitic acid, and is resistant to endoglycosidase H (Endo H). Most of the arrested G protein is also sensitive to digestion with neuraminidase, indicating that it has undergone at least partial sialylation. A minority of G protein accumulates under these conditions in a less-mature form, suggesting its inability to reach the mid-Golgi compartment. The oligosaccharides of this G protein are Endo-H-sensitive and seem to be partly trimmed. Whereas sialylated G protein was arrested intracellularly, fucose-labelled G protein was able to complete its transport to the cell surface, indicating that a late CCCP-sensitive step separates sialylation from fucosylation. These post-translational modifications indicate that G protein can be transported as far as the trans-Golgi in the presence of CCCP and is not merely arrested in the endoplasmic reticulum.

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Zhang, Xiaopei, Wei Wang, Weidong Zhu, Jie Dong, Yingying Cheng, Zujun Yin, and Fafu Shen. "Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels." International Journal of Molecular Sciences 20, no. 22 (November 8, 2019): 5573. http://dx.doi.org/10.3390/ijms20225573.

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Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways. They play important roles in biological processes such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing, and mRNA translation. lncRNAs have important functions in plant growth and development; biotic and abiotic stress responses; and in regulation of cell differentiation, the cell cycle, and the occurrence of many diseases in humans and animals. In this review, we summarize the functions and mechanisms of lncRNAs in plants, humans, and animals at different regulatory levels.

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Wild, Gary E., Patrizia Papalia, Mark J. Ropeleski, Julio Faria, and Alan BR Thomson. "Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part C: Protein Synthesis and Post-Translational Processing in Eukaryotic Cells." Canadian Journal of Gastroenterology 14, no. 7 (2000): 603–16. http://dx.doi.org/10.1155/2000/198641.

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The translation of mRNA constitutes the first step in the synthesis of a functional protein. The polypeptide chain is subsequently folded into the appropriate three-dimensional configuration and undergoes a variety of processing steps before being converted into its active form. These processing steps are intimately related to the cellular events that occur in the endoplasmic reticulum and Golgi compartments, and determine the sorting and transport of different proteins to their appropriate destinations within the cell. While the regulation of gene expression occurs primarily at the level of transcription, the expression of many genes can also be controlled at the level of translation. Most proteins can be regulated in response to extracellular signals. In addition, intracellular protein levels can be controlled by differential rates of protein degradation. Thus, the regulation of both the amounts and activities of intracellular proteins ultimately determines all aspects of cell behaviour.

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Steinbrenner, Holger, Lirija Alili, Dominik Stuhlmann, Helmut Sies, and Peter Brenneisen. "Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells." Biological Chemistry 388, no. 10 (October 1, 2007): 1043–51. http://dx.doi.org/10.1515/bc.2007.136.

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Abstract Selenoprotein P (SeP) is a highly glycosylated plasma protein containing up to 10 selenocysteine residues. It is secreted by hepatocytes and also by the human hepatoma cell line HepG2. Pharmacological inhibitors interfering with N-glycosylation, intracellular trafficking and calcium homeostasis were applied to examine post-translational processing and secretion of SeP by HepG2 cells. In parallel, the prototypic secretory glycoprotein α1-antitrypsin was used as technical control. Secretion of SeP was stimulated by increasing the extracellular calcium concentration and by inhibiting the release of sequestered calcium through dantrolene or U-73122. In contrast, brefeldin A and thapsigargin suppressed SeP secretion. Tunicamycin and monensin induced the synthesis of truncated non-glycosylated and partially glycosylated forms of SeP, which were secreted in spite of their impaired glycosylation. Both non-glycosylated and partially glycosylated SeP is utilised as selenium donor by target cells: impaired glycosylation affected neither the ability of SeP to induce the synthesis of the selenoenzyme cytosolic glutathione peroxidase nor its capacity to protect endothelial cells from oxidative stress.

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Staines, Katherine A., Vicky E. MacRae, and Colin Farquharson. "The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling." Journal of Endocrinology 214, no. 3 (June 13, 2012): 241–55. http://dx.doi.org/10.1530/joe-12-0143.

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The small integrin-binding ligand N-linked glycoprotein (SIBLING) family consists of osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. These proteins share many structural characteristics and are primarily located in bone and dentin. Accumulating evidence has implicated the SIBLING proteins in matrix mineralisation. Therefore, in this review, we discuss the individual role that each of the SIBLING proteins has in this highly orchestrated process. In particular, we emphasise how the nature and extent of their proteolytic processing and post-translational modification affect their functional role. Finally, we describe the likely roles of the SIBLING proteins in clinical disorders of hypophosphataemia and their potential therapeutic use.

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Mózner, Orsolya, Zsuzsa Bartos, Boglárka Zámbó, László Homolya, Tamás Hegedűs, and Balázs Sarkadi. "Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism." Cells 8, no. 10 (October 8, 2019): 1215. http://dx.doi.org/10.3390/cells8101215.

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The human ABCG2 is an important plasma membrane multidrug transporter, involved in uric acid secretion, modulation of absorption of drugs, and in drug resistance of cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and trafficking, have been shown to cause gout and increased drug toxicity. In this paper, we overview the key cellular pathways involved in the processing and trafficking of large membrane proteins, focusing on ABC transporters. We discuss the information available for disease-causing polymorphic variants and selected mutations of ABCG2, causing increased degradation and impaired travelling of the transporter to the plasma membrane. In addition, we provide a detailed in silico analysis of an as yet unrecognized loop region of the ABCG2 protein, in which a recently discovered mutation may actually promote ABCG2 membrane expression. We suggest that post-translational modifications in this unstructured loop at the cytoplasmic surface of the protein may have special influence on ABCG2 processing and trafficking.

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Matsuura, Yuichi, Yukinobu Tohya, Mihoko Onuma, Frank Roerink, Masami Mochizuki, and Takaaki Sugimura. "Expression and processing of the canine calicivirus capsid precursor." Microbiology 81, no. 1 (January 1, 2000): 195–99. http://dx.doi.org/10.1099/0022-1317-81-1-195.

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The ORF2 product of canine calicivirus (CaCV) was identified and its processing in mammalian cells was analysed. Immunoblot analysis revealed the presence of the 75 kDa capsid precursor in addition to a 57 kDa capsid protein and a 22 kDa N-terminal polypeptide in CaCV-infected cells treated at an elevated temperature. When the CaCV ORF2 was expressed in a transient mammalian expression system, only the 75 kDa precursor was detected in immunoblot analysis, suggesting that no post-translational processing occurred in this system. However, the precursor was processed to a 57 kDa protein and a 22 kDa polypeptide by the proteinase of feline calicivirus (FCV) when this was co-expressed with ORF2. Processing was blocked by site-directed mutagenesis of the putative cleavage site in the capsid precursor. The results indicate that the proteinase of FCV can cleave the capsid precursor of CaCV to produce the mature capsid protein and that CaCV may have a similar proteinase.

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Papa, Sergio, Salvatore Scacco, Domenico De Rasmo, Anna Signorile, Francesco Papa, Damiano Panelli, Annarita Nicastro, et al. "cAMP dependent protein kinase regulates expression and post-translational processing of respiratory chain complex I in mammalian cells." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1797 (July 2010): 10. http://dx.doi.org/10.1016/j.bbabio.2010.04.047.

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van Amstel, Hans K. Ploos, A. Linda van der Zanden, Pieter H. Reitsma, and Rogier M. Bertina. "Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus sequences for the post-translational processing." FEBS Letters 222, no. 1 (September 28, 1987): 186–90. http://dx.doi.org/10.1016/0014-5793(87)80217-x.

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García-Martínez, A., D. A. Cano, A. Flores-Martínez, J. Gil, M. Puig-Domingo, S. M. Webb, A. Soto-Moreno, and A. Picó. "Why don’t corticotroph tumors always produce Cushing’s disease?" European Journal of Endocrinology 181, no. 3 (September 2019): 351–61. http://dx.doi.org/10.1530/eje-19-0338.

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Objective Silent corticotroph tumors are a pituitary neuroendocrine tumor subtype of corticotroph lineage that do not clinically express Cushing’s disease. The silencing of this type of tumor is not fully understood. The aim of the present study was to delve into the lack of secretory activity, studying the post-transcriptional and post-translational regulation of POMC/ACTH in a series of molecularly identified functioning and silent corticotroph tumors. Design We analyzed 24 silent corticotroph, 23 functioning corticotroph and 25 silent gonadotroph tumors. Methods We used Sanger sequencing, quantitative real-time PCR and Western blot to analyze genetic alterations in POMC, gene expression of TBX19, NEUROD1, POMC, PCSK1, PCSK2, CPE and PAM and protein expression of POMC, PC1/3, PC2, CPE and PAM. Results We found different polymorphisms in the POMC gene of corticotroph tumors, some of them related to deficiency of proopiomelanocortin. Silent corticotroph tumors showed lower PC1/3 gene and protein expression than functioning ones, especially compared to micro-functioning corticotroph tumors (all P < 0.05). Moreover, we found a positive correlation between PC2 and CPE gene and protein expression (rho ≥ 0.670, P < 0.009) in silent corticotroph tumors compared with functioning ones. Conclusions By studying the post-transcriptional and post-translational processing of POMC and ACTH, respectively, in a large series of silent and functioning corticotroph tumors, we found that the lack of secretory activity of these tumors is related to an impaired processing of POMC and a high degradation of ACTH, with the macro-functioning corticotroph tumor behaving as an intermediate state between micro-functioning and silent corticotroph tumors.

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EDGE, Albert S. B. "Deglycosylation of glycoproteins with trifluoromethanesulphonic acid: elucidation of molecular structure and function." Biochemical Journal 376, no. 2 (December 1, 2003): 339–50. http://dx.doi.org/10.1042/bj20030673.

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The alteration of proteins by post-translational modifications, including phosphorylation, sulphation, processing by proteolysis, lipid attachment and glycosylation, gives rise to a broad range of molecules that can have an identical underlying protein core. An understanding of glycosylation of proteins is important in clarifying the nature of the numerous variants observed and in determining the biological roles of these modifications. Deglycosylation with TFMS (trifluoromethanesulphonic acid) [Edge, Faltynek, Hof, Reichert, and Weber, (1981) Anal. Biochem. 118, 131–137] has been used extensively to remove carbohydrate from glycoproteins, while leaving the protein backbone intact. Glycosylated proteins from animals, plants, fungi and bacteria have been deglycosylated with TFMS, and the most extensively studied types of carbohydrate chains in mammals, the N-linked, O-linked and glycosaminoglycan chains, are all removed by this procedure. The method is based on the finding that linkages between sugars are sensitive to cleavage by TFMS, whereas the peptide bond is stable and is not broken, even with prolonged deglycosylation. The relative susceptibility of individual sugars in glycosidic linkage varies with the substituents at C-2 and the occurrence of amido and acetyl groups, but even the most stable sugars are removed under conditions that are sufficiently mild to prevent scission of peptide bonds. The post-translational modifications of proteins have been shown to be required for diverse biological functions, and selective procedures to remove these modifications play an important role in the elucidation of protein structure and function.

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Pagliaro, Luca, Claudia Sorrentino, and Giovanni Roti. "Targeting Notch Trafficking and Processing in Cancers." Cells 9, no. 10 (September 29, 2020): 2212. http://dx.doi.org/10.3390/cells9102212.

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The Notch family comprises a group of four ligand-dependent receptors that control evolutionarily conserved developmental and homeostatic processes and transmit signals to the microenvironment. NOTCH undergoes remodeling, maturation, and trafficking in a series of post-translational events, including glycosylation, ubiquitination, and endocytosis. The regulatory modifications occurring in the endoplasmic reticulum/Golgi precede the intramembrane γ-secretase proteolysis and the transfer of active NOTCH to the nucleus. Hence, NOTCH proteins coexist in different subcellular compartments and undergo continuous relocation. Various factors, including ion concentration, enzymatic activity, and co-regulatory elements control Notch trafficking. Interfering with these regulatory mechanisms represents an innovative therapeutic way to bar oncogenic Notch signaling. In this review, we briefly summarize the role of Notch signaling in cancer and describe the protein modifications required for NOTCH to relocate across different subcellular compartments. We focus on the functional relationship between these modifications and the corresponding therapeutic options, and our findings could support the development of trafficking modulators as a potential alternative to the well-known γ-secretase inhibitors.

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Sui, Xin, and Yi-Ming Li. "Development of Ubiquitin Tools for Studies of Complex Ubiquitin Processing Protein Machines." Current Organic Chemistry 23, no. 23 (January 9, 2020): 2614–25. http://dx.doi.org/10.2174/1385272823666191113161511.

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: Ubiquitination is one of the most extensive post-translational modifications in eukaryotes and is involved in various physiological processes such as protein degradation, autophagy, protein interaction, and protein localization. The ubiquitin (Ub)-related protein machines include Ub-activating enzymes (E1s), Ub-conjugating enzymes (E2s), Ub ligases (E3s), deubiquitinating enzymes (DUBs), p97, and the proteasomes. In recent years, the role of DUBs has been extensively studied and relatively well understood. On the other hand, the functional mechanisms of the other more complex ubiquitin-processing protein machines (e.g., E3, p97, and proteasomes) are still to be sufficiently well explored due to their intricate nature. One of the hurdles facing the studies of these complex protein machines is the challenge of developing tailor-designed structurally defined model substrates, which unfortunately cannot be directly obtained using recombinant technology. Consequently, the acquisition and synthesis of the ubiquitin tool molecules are essential for the elucidation of the functions and structures of the complex ubiquitin-processing protein machines. This paper aims to highlight recent studies on these protein machines based on the synthetic ubiquitin tool molecules.

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Robinson, A., and B. Austen. "The role of topogenic sequences in the movement of proteins through membranes." Biochemical Journal 246, no. 2 (September 1, 1987): 249–61. http://dx.doi.org/10.1042/bj2460249.

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Recent advances have led to considerable convergence in ideas of the way topogenic sequences act to translocate proteins across various intracellular membranes (Table 2). Whereas co-translational translocation and processing were previously considered the norm at the endoplasmic reticulum membrane, several instances of post-translational translocation into endoplasmic reticulum microsomes in vitro have now been described. However, it must be noted that post-translational translocation in vitro is much less efficient than when endoplasmic reticulum membranes are present during translation, and it is possible that in the intact cell translocation occurs during translation. Movement of proteins into chloroplasts and mitochondria occurs after translation. When translocation is post-translational, proteins may perhaps traverse the membrane as folded domains, and the conformational effects of topogenic sequences on these domains may be as envisaged in Wickner's ‘membrane-trigger hypothesis’. Both signal and transit sequences possess amphipathic structures which are capable of interacting with phospholipid bilayers, and these interactions may disturb the bilayer sufficiently to allow entry of the following domains of protein. There is increasing evidence that GTP is required to bind ribosomes and their associated nascent chains to the endoplasmic reticulum membrane. Precisely how the cell's energy is applied to achieve translocation is not clear, but one possibility at the endoplasmic reticulum is that a GTP-hydrolysing transducing mechanism may exist to couple signal sequence receptor binding to movement of the nascent chain across the membrane. Electrochemical gradients are required for protein movement to the mitochondrial inner membrane and across the bacterial inner membrane. Cytoplasmic factors such as SRP, the secA gene product or a 40 kDa protein (for mitochondrial precursors) may act by binding to topogenic sequences and preventing precursor proteins as they are translated from folding into forms which cannot be translocated. Specificity in the cell may be achieved both by targetting interactions between these cytoplasmic factors and their receptors located in target membranes, and also by specific binding of the topogenic sequences to specific proteins integrated into the target membranes. Possible candidates for the latter are the protein of microsomal membranes that reacts with a photoreactive signal peptide to give a 45 kDa complex (Fig. 1), the secY gene product of the bacterial inner membrane, and receptors on the outer membranes of chloroplasts and mitochondria. Whether these aid translocation as well as recognition is not clear.(ABSTRACT TRUNCATED AT 400 WORDS)

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Carpio, Marcos A., Cecilia López Sambrooks, Edith S. Durand, and Marta E. Hallak. "The arginylation-dependent association of calreticulin with stress granules is regulated by calcium." Biochemical Journal 429, no. 1 (June 14, 2010): 63–72. http://dx.doi.org/10.1042/bj20091953.

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Post-translational modifications of proteins are important for the regulation of cell functions; one of these modifications is post-translational arginylation. In the present study, we show that cytoplasmic CRT (calreticulin) is arginylated by ATE1 (arginyl-tRNA protein transferase). We also show that a pool of CRT undergoes retrotranslocation from the ER (endoplasmic reticulum) to the cytosol, because in CRT-knockout cells transfected with full-length CRT (that has the signal peptide), cytoplasmic CRT appears as a consequence of its expression and processing in the ER. After the cleavage of the signal peptide, an N-terminal arginylatable residue is revealed prior to retrotranslocation to the cytoplasm where arginylation takes place. SGs (stress granules) from ATE1-knockout cells do not contain CRT, indicating that CRT arginylation is required for its association to SGs. Furthermore, R-CRT (arginylated CRT) in the cytoplasm associates with SGs in cells treated with several stressors that lead to a reduction of intracellular Ca2+ levels. However, in the presence of stressors that do not affect Ca2+ levels, R-CRT is not recruited to these loci despite the fact that SGs are formed, demonstrating Ca2+-dependent R-CRT association to SGs. We conclude that post-translational arginylation of retrotranslocated CRT, together with the decrease in intracellular Ca2+, promotes the association of CRT to SGs.

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Journal articles on the topic 'Post-Translational Protein Processing'

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