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Academic literature on the topic 'Transactivating domain'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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Journal articles on the topic "Transactivating domain"

1

MOREL, Yannick, and Robert BAROUKI. "The repression of nuclear factor I/CCAAT transcription factor (NFI/CTF) transactivating domain by oxidative stress is mediated by a critical cysteine (Cys-427)." Biochemical Journal 348, no. 1 (May 9, 2000): 235–40. http://dx.doi.org/10.1042/bj3480235.

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The activity of the nuclear factor I/CCAAT transcription factor (NFI/CTF) is negatively regulated by oxidative stress. The addition of relatively high (millimolar) H2O2 concentrations inactivates cellular NFI DNA-binding activity whereas lower concentrations can repress NFI/CTF transactivating function. We have investigated the mechanism of this regulation using Gal4 fusion proteins and transfection assays. We show that micromolar H2O2 concentrations repress the transactivating domain of NFI/CTF in a dose-dependent manner and are less or not active on other transcription factors' transactivating domains. Studies using deletions and point mutations pointed to the critical role of Cys-427. Indeed, when this cysteine is mutated into a serine, the repression by H2O2 is totally blunted. Mutation of other cysteine, serine and tyrosine residues within the transactivating domain had no clear effect on the repression by H2O2. Finally, treatment of cells with the thiol-alkylating reagent N-ethylmaleimide leads to a decrease in the transactivating function, which is dependent on Cys-427. This study shows that transactivating domains of transcription factors can constitute very sensitive targets of oxidative stress and highlights the critical role of these domains.

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Becker, D. M., S. M. Hollenberg, and R. P. Ricciardi. "Fusion of adenovirus E1A to the glucocorticoid receptor by high-resolution deletion cloning creates a hormonally inducible viral transactivator." Molecular and Cellular Biology 9, no. 9 (September 1989): 3878–87. http://dx.doi.org/10.1128/mcb.9.9.3878.

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The 289-amino-acid E1A protein of adenovirus type 2 stimulates transcription from early viral and certain cellular promoters. Its mechanism is not known, and there exist no temperature-sensitive mutants of E1A that could help to elucidate the details of E1A transcriptional activation. To create for E1A such a conditional phenotype, we fused portions of E1A to the human glucocorticoid receptor (GR) to make transactivation by E1A dependent on the presence of dexamethasone. Nested subsets of the E1A coding region, centered around the 46-amino-acid transactivating domain, were substituted for the DNA-binding domain of the GR. One of the resulting chimeric proteins (GR/E1A-99), which included the entire E1A transactivating domain, stimulated expression from a viral early promoter (E3) exclusively in the presence of hormone. GR/E1A-99 did not transactivate a GR-responsive promoter. It therefore exhibited the promoter specificity of E1A while possessing the hormone inducibility of the GR. Two smaller chimeras that contained only portions of the E1A transactivating domain failed to transactivate E3. These three chimeras were constructed by a novel strategy, high-resolution deletion cloning. In this procedure, series of unidirectional deletions were made with exonuclease III on each side of the E1A coding region at a resolution of 1 to 2 nucleotides. The large number of in-frame fragments present in the collection of deleted clones facilitated the construction of the GR/E1A chimeras and can be used to create many additional fusions.

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Becker, D. M., S. M. Hollenberg, and R. P. Ricciardi. "Fusion of adenovirus E1A to the glucocorticoid receptor by high-resolution deletion cloning creates a hormonally inducible viral transactivator." Molecular and Cellular Biology 9, no. 9 (September 1989): 3878–87. http://dx.doi.org/10.1128/mcb.9.9.3878-3887.1989.

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The 289-amino-acid E1A protein of adenovirus type 2 stimulates transcription from early viral and certain cellular promoters. Its mechanism is not known, and there exist no temperature-sensitive mutants of E1A that could help to elucidate the details of E1A transcriptional activation. To create for E1A such a conditional phenotype, we fused portions of E1A to the human glucocorticoid receptor (GR) to make transactivation by E1A dependent on the presence of dexamethasone. Nested subsets of the E1A coding region, centered around the 46-amino-acid transactivating domain, were substituted for the DNA-binding domain of the GR. One of the resulting chimeric proteins (GR/E1A-99), which included the entire E1A transactivating domain, stimulated expression from a viral early promoter (E3) exclusively in the presence of hormone. GR/E1A-99 did not transactivate a GR-responsive promoter. It therefore exhibited the promoter specificity of E1A while possessing the hormone inducibility of the GR. Two smaller chimeras that contained only portions of the E1A transactivating domain failed to transactivate E3. These three chimeras were constructed by a novel strategy, high-resolution deletion cloning. In this procedure, series of unidirectional deletions were made with exonuclease III on each side of the E1A coding region at a resolution of 1 to 2 nucleotides. The large number of in-frame fragments present in the collection of deleted clones facilitated the construction of the GR/E1A chimeras and can be used to create many additional fusions.

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TOLNAY, Mate, Yuang-Taung JUANG, and George C. TSOKOS. "Protein kinase A enhances, whereas glycogen synthase kinase-3β inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein D in a hierarchical fashion." Biochemical Journal 363, no. 1 (March 22, 2002): 127–36. http://dx.doi.org/10.1042/bj3630127.

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Heterogeneous nuclear ribonucleoprotein D (hnRNP D) is implicated in transcriptional regulation. Alternative splicing of exons 2 and 7 generates four isoforms of the protein. We report here that only isoforms that contain the product of exon 2 (amino acids 79–97) were able to transactivate. Moreover, the exon 2-encoded protein domain alone was sufficient to drive transcription. TATA-binding protein and p300 interacted with a synthetic peptide corresponding to exon 2, and both proteins co-precipitated with hnRNP D. Stimulation of protein kinase A (PKA) and protein kinase C (PKC) synergistically induced the transactivating ability of hnRNP D, and the exon 2-encoded domain was sufficient for this inducibility. In kinase assays PKA phosphorylated Ser-87 of hnRNP D, whereas glycogen synthase kinase-3β (GSK-3β) phosphorylated Ser-83, but only if Ser-87 had been pre-phosphorylated by PKA. Phosphorylation of Ser-87 enhanced, whereas phosphorylation of Ser-83 repressed, transactivation. Overexpression of GSK-3β inhibited transactivation by hnRNP D, but stimulation of PKC negated the inhibitory effect of GSK-3β. We suggest that a hierarchical phosphorylation pathway regulates the transactivating ability of hnRNP D: PKA activates hnRNP D, but at the same time renders it sensitive to inhibition by GSK-3β; the latter inhibition can be suspended by inactivating GSK-3β with PKC.

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Bisaillon, Richard, Brian T. Wilhelm, Jana Krosl, and Guy Sauvageau. "C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating oncoprotein." Blood 118, no. 17 (October 27, 2011): 4682–89. http://dx.doi.org/10.1182/blood-2011-05-354076.

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Abstract The three-amino-acid loop extension (TALE) class homeodomain proteins MEIS1 and PKNOX1 (PREP1) share the ability to interact with PBX and HOX family members and bind similar DNA sequences but appear to play opposing roles in tumor development. Elevated levels of MEIS1 accelerate development of HOX- and MLL-induced leukemias, and this pro-tumorigenic property has been associated with transcriptional activity of MEIS1. In contrast, reduction of PKNOX1 levels has been linked with cancer development despite the absence of an identifiable transactivating domain. In this report, we show that a chimeric protein generated by fusion of the MEIS1 C-terminal region encompassing the transactivating domain with the full-length PKNOX1 (PKNOX1-MC) acquired the ability to accelerate the onset of Hoxa9-induced leukemia in the mouse bone marrow transduction/transplantation model. Gene expression profiling of primary bone marrow cells transduced with Hoxa9 plus Meis1, or Hoxa9 plus Pknox1-MC revealed perturbations in overlapping functional gene subsets implicated in DNA packaging, chromosome organization, and in cell cycle regulation. Together, results presented in this report suggest that the C-terminal domain of MEIS1 confers to PKNOX1 an ectopic transactivating function that promotes leukemogenesis by regulating expression of genes involved in chromatin accessibility and cell cycle progression.

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Simcha, Inbal, Michael Shtutman, Daniela Salomon, Jacob Zhurinsky, Einat Sadot, Benjamin Geiger, and Avri Ben-Ze'ev. "Differential Nuclear Translocation and Transactivation Potential of β-Catenin and Plakoglobin." Journal of Cell Biology 141, no. 6 (June 15, 1998): 1433–48. http://dx.doi.org/10.1083/jcb.141.6.1433.

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β-Catenin and plakoglobin are homologous proteins that function in cell adhesion by linking cadherins to the cytoskeleton and in signaling by transactivation together with lymphoid-enhancing binding/T cell (LEF/TCF) transcription factors. Here we compared the nuclear translocation and transactivation abilities of β-catenin and plakoglobin in mammalian cells. Overexpression of each of the two proteins in MDCK cells resulted in nuclear translocation and formation of nuclear aggregates. The β-catenin-containing nuclear structures also contained LEF-1 and vinculin, while plakoglobin was inefficient in recruiting these molecules, suggesting that its interaction with LEF-1 and vinculin is significantly weaker. Moreover, transfection of LEF-1 translocated endogenous β-catenin, but not plakoglobin to the nucleus. Chimeras consisting of Gal4 DNA-binding domain and the transactivation domains of either plakoglobin or β-catenin were equally potent in transactivating a Gal4-responsive reporter, whereas activation of LEF-1– responsive transcription was significantly higher with β-catenin. Overexpression of wild-type plakoglobin or mutant β-catenin lacking the transactivation domain induced accumulation of the endogenous β-catenin in the nucleus and LEF-1–responsive transactivation. It is further shown that the constitutive β-catenin–dependent transactivation in SW480 colon carcinoma cells and its nuclear localization can be inhibited by overexpressing N-cadherin or α-catenin. The results indicate that (a) plakoglobin and β-catenin differ in their nuclear translocation and complexing with LEF-1 and vinculin; (b) LEF-1–dependent transactivation is preferentially driven by β-catenin; and (c) the cytoplasmic partners of β-catenin, cadherin and α-catenin, can sequester it to the cytoplasm and inhibit its transcriptional activity.

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Inukai, Takeshi, Toshiya Inaba, Satoshi Ikushima, and A. Thomas Look. "The AD1 and AD2 Transactivation Domains of E2A Are Essential for the Antiapoptotic Activity of the Chimeric Oncoprotein E2A-HLF." Molecular and Cellular Biology 18, no. 10 (October 1, 1998): 6035–43. http://dx.doi.org/10.1128/mcb.18.10.6035.

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ABSTRACT The chimeric oncoprotein E2A-HLF, generated by the t(17;19) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia, incorporates the transactivation domains of E2A and the basic leucine zipper (bZIP) DNA-binding and protein dimerization domain of HLF (hepatic leukemic factor). The ability of E2A-HLF to prolong the survival of interleukin-3 (IL-3)-dependent murine pro-B cells after IL-3 withdrawal suggests that it disrupts signaling pathways normally responsible for cell suicide, allowing the cells to accumulate as transformed lymphoblasts. To determine the structural motifs that contribute to this antiapoptotic effect, we constructed a panel of E2A-HLF mutants and programmed their expression in IL-3-dependent murine pro-B cells (FL5.12 line), using a zinc-inducible vector. Neither the E12 nor the E47 product of the E2A gene nor the wild-type HLF protein was able to protect the cells from apoptosis induced by IL-3 deprivation. Surprisingly, different combinations of disabling mutations within the HLF bZIP domain had little effect on the antiapoptotic property of the chimeric protein, so long as the amino-terminal portion of E2A remained intact. In the context of a bZIP domain defective in DNA binding, mutants retaining either of the two transactivation domains of E2A were able to extend cell survival after growth factor deprivation. Thus, the block of apoptosis imposed by E2A-HLF in pro-B lymphocytes depends critically on the transactivating regions of E2A. Since neither DNA binding nor protein dimerization through the bZIP domain of HLF is required for this effect, we propose mechanisms whereby protein-protein interactions with the amino-terminal region of E2A allow the chimera to act as a transcriptional cofactor to alter the expression of genes regulating the apoptotic machinery in pro-B cells.

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Kusano, Shuichi, Yuki Shiimura, and Yoshito Eizuru. "I-mfa domain proteins specifically interact with SERTA domain proteins and repress their transactivating functions." Biochimie 93, no. 9 (September 2011): 1555–64. http://dx.doi.org/10.1016/j.biochi.2011.05.016.

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Zaragoza, Michael V., Lisa E. Lewis, Guifeng Sun, Eric Wang, Ling Li, Ilham Said-Salman, Laura Feucht, and Taosheng Huang. "Identification of the TBX5 transactivating domain and the nuclear localization signal." Gene 330 (April 2004): 9–18. http://dx.doi.org/10.1016/j.gene.2004.01.017.

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Whitelaw, M. L., J. A. Gustafsson, and L. Poellinger. "Identification of transactivation and repression functions of the dioxin receptor and its basic helix-loop-helix/PAS partner factor Arnt: inducible versus constitutive modes of regulation." Molecular and Cellular Biology 14, no. 12 (December 1994): 8343–55. http://dx.doi.org/10.1128/mcb.14.12.8343.

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Gene regulation by dioxins is mediated via the dioxin receptor, a ligand-dependent basic helix-loop-helix (bHLH)/PAS transcription factor. The latent dioxin receptor responds to dioxin signalling by forming an activated heterodimeric complex with a specific bHLH partner, Arnt, an essential process for target DNA recognition. We have analyzed the transactivating potential within this heterodimeric complex by dissecting it into individual subunits, replacing the dimerization and DNA-binding bHLH motifs with heterologous zinc finger DNA-binding domains. The uncoupled Arnt chimera, maintaining 84% of Arnt residues, forms a potent and constitutive transcription factor. Chimeric proteins show that the dioxin receptor also harbors a strong transactivation domain in the C terminus, although this activity was silenced by inclusion of 82 amino acids from the central ligand-binding portion of the dioxin receptor. This central repression region conferred binding of the molecular chaperone hsp90 upon otherwise constitutive chimeras in vitro, indicating that hsp90 has the ability to mediate a cis-repressive function on distant transactivation domains. Importantly, when the ligand-binding domain of the dioxin receptor remained intact, the ability of this hsp90-binding activity to confer repression became conditional rather than irreversible. Our data are consistent with a model in which crucial activities of the dioxin receptor, such as dimerization with Arnt and transactivation, are conditionally repressed by the central ligand- and-hsp90-binding region of the receptor. In contrast, the Arnt protein appears to be free from any repressive activity. Moreover, within the context of the dioxin response element (xenobiotic response element), the C terminus of Arnt conferred a potent, dominating transactivation function onto the native bHLH heterodimeric complex. Finally, the relative transactivation potencies of the individual dioxin receptor and Arnt chimeras varied with cell type and promoter architecture, indicating that the mechanisms for transcriptional activation may differ between these two subunits and that in the native complex the transactivation pathway may be dependent upon cell-specific and promoter contexts.

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Dissertations / Theses on the topic "Transactivating domain"

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Ramakrishnan, Venkatesh. "Structural analysis of a transactivation domain cofactor complex." Doctoral thesis, [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976325381.

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Betney, Russell. "Mutational analysis of the human androgen receptor transactivation domain." Thesis, University of Aberdeen, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401515.

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Mutants were created within the main activation function domain to investigate the structure and function of this region. Structural studies based on limited proteolysis and fluorescence spectroscopy experiments, indicate that though the N-terminus is not as specially structured as either the LBD or DBD, there are regions of specific folding within the activation domain. Results from in silco investigation suggest several possible regions of a helix within the AF-1 domain, and mutants designed to disrupt these regions were less folded than the wild-type protein. Protein-protein interaction studies showed that the four mutants designed to potentially disrupt function rather than structure, had reduced binding to the large subunit of TFIIF - RAP74, but had no effect on binding to the transcriptional co-activator SRC-1a. In a functional assay performed in yeast cells, these four same mutants all showed reduced activity, showing the same trend as binding to RAP74. This could be an indication that the function of the AR is dependent upon binding to the general transcription factor TFIIF. Interestingly one of the mutants that was found to show increased structure over the wild-type protein was previously shown to have a reduced interaction with RAP74. This implies that structure is important for interaction with the transcription machinery. This was confirmed by FTIR experiments which can detect changes in the proportion of secondary structure present in a protein. These data show that the proportion of a helix present in the AF-1 domain increases when it is complexed with RAP74. GST pull-down assays then demonstrated that the complex of AF-1 and RAP74 enhanced the binding of the co-activator SRC-1a. This is the first time that this cooperativity has been demonstrated with nuclear receptors and interacting proteins. Additionally, specific phosphorylation of the AF-1 domain by glycogen synthase kinase 3 also increases the level of binding with SRC-1a. These data together suggest a possible mechanism of action for the androgen receptor and its involvement in regulating transcription.

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Seth, Alpna. "Functional Analysis of the c-MYC Transactivation Domain: A Dissertation." eScholarship@UMMS, 1992. https://escholarship.umassmed.edu/gsbs_diss/315.

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Many polypeptide growth factors act by binding to cell surface receptors that have intrinsic tyrosine kinase activity. Binding of these growth factors to their cognate receptors results in the initiation of mitogenic signals which then get transduced to the interior of the cell. A critical target for extracellular signals is the nucleus. A plethora of recent evidence indicates that extracellular signals can affect nuclear gene expression by modulating transcription factor activity. In this study, I have determined that the transactivation domain of c-Myc (protein product of the c-myc proto-oncogene) is a direct target of mitogen-activated signaling pathways involving protein kinases. Further, my study demonstrates that transactivation of gene expression by c-Myc is regulated as a function of the cell cycle. c-Myc is a sequence-specific DNA binding protein that forms leucine zipper complexes and can act as a transcription factor. Although, significant progress has been made in understanding the cellular properties of c-Myc, the precise molecular mechanism of c-Myc function in oncogenesis and in normal cell growth is not known. I have focused my attention on the property of c-Myc to function as a sequence-specific transcription factor. In my studies, I have employed a fusion protein strategy, where the transactivation domain of the transcription factor c-Myc is fused to the DNA binding domain and nuclear localization signal of the yeast transcription factor GAL4. This fusion protein was expressed together with a plasmid consisting of specific GAL4 binding sites cloned upstream of a minimal E1b promoter and a reporter gene. The activity of the c-Myc transactivation domain was measured as reporter gene activity in cell extracts. This experimental approach enabled me to directly monitor the activity of the c-Myc transactivation domain. Results listed in Chapter II demonstrate that the transactivation domain of c-Myc at Ser-62 is a target of regulation by mitogen-stimulated signaling pathways. Furthermore, I have determined that a mitogen activated protein kinase, p41mapk, can phosphorylate the c-Myc transactivation domain at Ser-62. Phosphorylation at this site results in a marked increase in transactivation of gene expression. A point mutation at the MAP kinase phosphorylation site (Ser-62) causes a decrease in transactivation. c-Myc expression is altered in many types of cancer cells, strongly implicating c-myc as a critical gene in cell growth control. The molecular mechanisms by which c-Myc regulates cellular proliferation are not understood. For instance, it is not clear where in the cell cycle c-Myc functions and what regulates its activity. In exponentially growing cells, the expression levels of c-Myc remain unchanged as the cells progress through the cell cycle. The function of c-Myc may therefore be regulated by a mechanism involving a post-translational modification, such as phosphorylation. Results described in chapter IV demonstrate that the level of c-Myc mediated transactivation oscillates as cells progress through the cell cycle and was greatly increased during the S to G2/M transition. Furthermore, mutation of the phosphorylation site Ser-62 in the c-Myc transactivation domain diminishes this effect, suggesting a functional role for this phosphorylation site in the cell cycle-specific regulation of c-Myc activity. Taken together, my dissertation study reveals a molecular mechanism for the regulation of nuclear gene expression in response to mitogenic stimuli.

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Borcherds, Wade Michael. "Structure, Dynamics, and Evolution of the Intrinsically Disordered p53 Transactivation Domain." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4640.

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in numerous disease states, including cancers and neurodegenerative diseases. All proteins are dynamic in nature, occupying a range of conformational flexibilities. This inherent flexibility is required for their function, with ordered proteins and IDPs representing the least flexible, and most flexible, respectively. As such IDPs possess little to no stable tertiary or secondary structure, they instead form broad ensembles of heterogeneous structures, which fluctuate over multiple time scales. Although IDPs often lack stable secondary structure they can assume a more stable structure in the presence of their binding partners in a coupled folding binding reaction. The phenomenon of the dynamic behavior of IDPs is believed to confer several functional advantages but remains poorly understood. To that end the dynamic and structural properties of a family of IDPs - p53 transactivation domains (TAD) was measured and compared with the sequence divergence. Interestingly we were able to find stronger correlations between the dynamic properties and the sequence divergence than between the structure and sequence, suggesting that the dynamic properties are the primary trait being xiii conserved by evolution. These correlations were strongest within clusters of the IDPs that correlated with known protein binding sites. Additionally, we show strong correlations between the several available disorder predictors and the backbone dynamics of this family of IDPs. This indicates the potential of predicting the dynamic behavior of proteins, which may be beneficial in future drug design. The limited number of atomic models currently determined for IDPs hampers understanding of how their amino acid sequences dictate the structural ensembles they adopt. The current dearth of atomic models for IDPs makes it difficult to test the following hypotheses: 1. The structural ensembles of IDPs are dictated by local interactions. 2. The structural ensembles of IDPs will be similar above a certain sequence identity threshold. Based on the premise that sequence determines structure, structural ensembles were determined and compared for a set of homologous IDPs. Utilizing orthologues allows for the identification of important structural features and behaviors by virtue of their conservation. A new methodology of creating ensembles was implemented that broadly samples conformational space. This allowed us to find recurring local structural features within the structural ensembles even between the more distantly related homologues that were processed. This method of ensemble creation is also the first method to show convergence of secondary structural characteristics between discrete ensembles.

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Powell, Anne Terese. "Structure and Dynamics of the p53 Transactivation Domain Binding to MDM2 and RPA70." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4207.

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The tumor suppressor protein, p53, is mutated or dysregulated in nearly all human cancers(1). The amino terminal domains are essential for transcriptional activation in stressed cells and play a vital role in cell cycle regulation, apoptosis and senescence. The transactivation (TAD) and proline rich domains in this region are dynamic and intrinsically disordered; lacking stable secondary or tertiary structure. This region contains multiple binding sites; arguably, the most significant of these is for p53's negative regulator, the E3 ligase, MDM2. An important, but less understood interaction involving the single stranded DNA binding protein, RPA70A, is hypothesized to be involved in maintaining genome integrity(2-4). Additionally, the amino terminus contains an important single nucleotide polymorphism that has demonstrated different affinity for MDM2 and is of significant biological importance in the induction of apoptosis (5). Isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy were employed to investigate how the thermodynamics and the inherent flexibility of the amino terminus of p53 play a role in complex formation with the MDM2 or RPA70 proteins. Understanding the structure, dynamics, and function of p53 is paramount in the fight against cancer.

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Poosapati, Anusha. "Disorder Levels of c-Myb Transactivation Domain Regulate its Binding Affinity to the KIX Domain of CREB Binding Protein." Scholar Commons, 2017. https://scholarcommons.usf.edu/etd/7436.

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Intrinsically disordered proteins (IDPs) do not form stable tertiary structures like their ordered partners. They exist as heterogeneous ensembles that fluctuate over a time scale. Intrinsically disordered regions and proteins are found across different phyla and exert crucial biological functions. They exhibit transient secondary structures in their free state and become folded upon binding to their protein partners via a mechanism called coupled folding and binding. Some IDPs form alpha helices when bound to their protein partners. We observed a set of cancer associated IDPs where the helical binding segments of IDPs are flanked by prolines on both the sides. Helix-breaking prolines are frequently found in IDPs flanking the binding segment and are evolutionarily conserved across phyla. Two studies have shown that helix flanking prolines modulate the function of IDPs by regulating the levels of disorder in their free state and in turn regulating the binding affinities to their partners. We aimed to study if this is a common phenomenon in IDPs that exhibit similar pattern in the conservation of helix flanking prolines. We chose to test the hypothesis in c-Myb-KIX : IDP-target system in which the disordered protein exhibits high residual helicity levels in its free state. c-Myb is a hematopoietic regulator that plays a crucial role in cancer by binding to the KIX domain of CBP. Studying the functional regulation of c-Myb by modulating the disorder levels in c-Myb and in IDPs in general provides a better understanding of the way IDPs function and can be used in therapeutic strategies as IDPs are known to be involved in regulating various cellular processes and diseases. To study the effect of conserved helix flanking prolines on the residual helicity levels of c-Myb and its binding affinity to the KIX domain of CBP, we mutated the prolines to alanines. Mutating prolines to alanines increased the helicity levels of c-Myb in its free state. This small increase in the helicity levels of a highly helical c-Myb showed almost no effect on the binding affinity between cMyb and KIX. We hypothesized that there is a helical threshold for coupled folding and binding beyond which helicity levels of the free state IDP have no effect on its binding to their ordered protein partner. To test this hypothesis, we mutated solvent exposed amino acid residues in c-Myb that reduce its overall helicity and studied its effect on the binding affinity between c-Myb and KIX. Over a broad range of reduction in helicity levels of the free state did not show an effect on the binding affinity but beyond a certain level, decrease in helicity levels showed pronounced effects on the binding affinity between c-Myb and KIX.

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Fischer, Katharina. "The mineralocorticoid receptor amino terminal transactivation domain investigation of structural plasticity and protein-protein interactions /." Thesis, Available from the University of Aberdeen Library & Historic Collections Digital Resources, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=24694.

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Thesis (Ph.D.)--Aberdeen University, 2008.
Title from web page (viewed on Feb. 23, 2009). With: Natural disordered sequences in the amino terminal domain of nuclear receptors : lessons from the androgen and glucocorticoid receptors / Iain J. McEwan ... et al. Nuclear Receptor Signalling. 2007: 5. Includes bibliographical references.

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Johnson, Thomas M. "p53 transactivation domain mutant knock-in mice provide novel insight into p53 tumor suppressor function /." May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.

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Reid, James Arthur. "Structural and functional analysis of the amino-terminal transactivation domain of the human androgen receptor." Thesis, University of Aberdeen, 2001. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU149342.

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The androgen receptor (AR) belongs to the steroid/nuclear receptor family of ligand-activated transcription factors. Most of these receptors activate transcription through two distinct regions known as activation functions (AF). The first, AF-1, is located within the variable amino-terminal domain (NTD) and the second, AF-2, within the ligand binding domain (LBD). However, the AR is unusual amongst the steroid receptor family in that an independent AF-2 function has not been demonstrated. Transactivation by the AR is therefore dependent primarily upon AF-1. Previous work in our laboratory has shown that an amino-terminal fragment of the AR (amino acids 142 to 485) is able to interact specifically with RAP74, the large subunit of general transcription factor TFIIF. Using a series of deletion constructs, two distinct AR binding sites have been identified with RAP74, one at the amino-terminus and one at the carboxyl-terminus of the protein. Functional analyses of these interactions suggest that the interaction between the AR and the carboxyl-terminus of RAP74 is the most significant with respect to transcriptional activation by the receptor. Mutational analysis of the AR-NTD identified a six amino acid motif, PSTLSL, as being involved in RAP74 binding. In addition to RAP74, an interaction has been identified between the p160 coactivator protein SRC-1a and amino acids 142-485 of the AR. Interestingly, another high related p160 coactivator protein, TIF2, showed little or no binding to this region of the receptor. Structural analysis, using circular dichroism and fluorescence spectroscopy and sensitivity to protease digestion, indicates that the AR-NTD exists in an extended conformation in aqueous solution but retains a propensity to fold into a more ordered structure in the presence of the hydrophobic solvent trifluoroethanolor the osmolyte trimethylamine-N-oxide. Significantly, RAP74 also confers protection to trypsin digestion, consistent with folding of the AR-NTD (aa 142 to 485) upon interaction with a target factor.

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Lavery, Derek Norman. "The amino-terminal transactivation domain of the human androgen receptor : protein-protein interactions and structural characteristics." Thesis, University of Aberdeen, 2007. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU490182.

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An important target protein for the AR-AF1 domain is Transcription Factor IIF (TFIIF). At initiation of transcription, TFIIF recruits additional basal transcription factors, stabilises the transcriptional complex and increases elongation efficiency. Using chromatin immunoprecipitation, it was observed that the AR occupied distinct regions of the prostate-specificantigen enhancer but did not migrate with the elongating transcriptional complex. The major subunit of TFAAF, RAP74, has previously been shown to interact with AR-AF1 by our laboratory and it was observed that AR-AF1 can interact with both terminal regions of RAP74. Now, by selectively disrupting helices that structure the globular RAP74 C-terminal domain it appears that AR-AF1 binds to a groove within this region and specific hydrophobic amino acids are important in this generation. The kinetics of RAP74/AR-AF1 interactions have not been determined using surface plasmon resonance. Interestingly, AR-AF1 interacts differently with N- and C-terminal regions of RAP74 and the overall affinities are in the nanomolar range. The structural properties of AR-AF1 were examined using both fluorescence spectroscopy and gel filtration chromatography. It was found that the transactivation domain is structurally flexible and exists in a conformation that is not random coil or globular suggesting that it may be a molten globule. AR-AF1 interacted weakly with 8-anilinonaphthalene-1-sulfonic acid, a hydrophobic probe used to characterise the molten globule folding state. Gel filtration chromatography indicates that AR-AF1 is ∼65 kDa and has a hydrodynamic radius of ∼36 Co much larger than predictions suggest. Surprisingly, by plotting these properties on "folding curves", AR-AF1 is positioned alongside molten globules.

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Books on the topic "Transactivating domain"

1

Majumdar, Sonali. Structural and functional divergence of the transcription factor Pit-1: Analysis of the pou and transactivation domains. Ottawa: National Library of Canada = Bibliothèque nationale du Canada, 1997.

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Book chapters on the topic "Transactivating domain"

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"Transactivation Domain." In Encyclopedia of Cancer, 3748. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_5894.

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"TRRP (transactivation/transformation-domain associated protein)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 2039. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_17541.

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"PTIP (PAX transactivation interacting domain protein)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 1598–99. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_13797.

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Shen, Howard C., and Gerhard A. Coetzee. "The Androgen Receptor: Unlocking the Secrets of Its Unique Transactivation Domain." In Vitamins & Hormones, 301–19. Elsevier, 2005. http://dx.doi.org/10.1016/s0083-6729(05)71010-4.

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Conference papers on the topic "Transactivating domain"

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Liu, Xiaorong, and Jianhan Chen. "Modulation of p53 Transactivation Domain Conformations by Ligand Binding and Cancer-Associated Mutations." In Pacific Symposium on Biocomputing 2020. WORLD SCIENTIFIC, 2019. http://dx.doi.org/10.1142/9789811215636_0018.

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Brand, Toni M., Mari Iida, Matthew J. Wleklinski, Neha Luthar, Megan M. Starr, and Deric L. Wheeler. "Abstract 4276: Mapping C-terminal transactivation domains of nuclear HER family receptor tyrosine kinases." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-4276.

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Wachtel, Marco, Katharina Benischke, and Beat W. Schäfer. "Abstract B56: A CRISPR/Cas9 domain screen identifies a small motif in the PAX3-FOXO1 transactivation domain relevant for tumor maintenance in alveolar rhabdomyosarcoma." In Abstracts: AACR Special Conference on the Advances in Pediatric Cancer Research; September 17-20, 2019; Montreal, QC, Canada. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.pedca19-b56.

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Lafargue, Audrey, Hailun Wang, Sivarajan T. Chettiar, Rajendra P. Gajula, Kekoa Taparra, Katriana Nugent, and Phuoc T. Tran. "Abstract 6060: The transactivation domain of TWIST1 is required for TWIST1-induced aggressiveness in non-small cell lung cancer." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-6060.

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Lafargue, Audrey, Hailun Wang, Sivarajan T. Chettiar, Rajendra P. Gajula, Caleb Smack, Ismaeel Siddiqui, Kekoa Taparra, et al. "Abstract PO-067: The transactivation domain of TWIST1 is required for TWIST1-induced aggressiveness in non-small cell lung cancer." In Abstracts: AACR Virtual Special Conference on Radiation Science and Medicine; March 2-3, 2021. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1557-3265.radsci21-po-067.

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Khan, Shagufta H., John A. Arnott, Hani Atamna, Nihal Ahmad, and Raj Kumar. "Abstract 4552: Naturally occurring osmolyte, trehalose induces a functionally active conformation in an intrinsically disordered transactivation function domain (AF1) of the Glucocorticoid Receptor." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4552.

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Reports on the topic "Transactivating domain"

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Attardi, Laura D., and Nitin Raj. Identifying p53 Transactivation Domain 1-Specific Inhibitors to Alleviate the Side Effects of Prostate Cancer Therapy. Fort Belvoir, VA: Defense Technical Information Center, September 2013. http://dx.doi.org/10.21236/ada593265.

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Attardi, Laura D., and Nitin Raj. Identifying p53 Transactivation Domain 1-Specific Inhibitors to Alleviate the Side Effects of Prostate Cancer Therapy. Fort Belvoir, VA: Defense Technical Information Center, October 2014. http://dx.doi.org/10.21236/ada617329.

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