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Journal articles on the topic 'Negative Elongation Factor complex'

Author: Grafiati

Published: 3 June 2025

Last updated: 31 July 2025

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1

Huang, Mengling, Abrar Ahmed, Wei Wang, et al. "Negative Elongation Factor (NELF) Inhibits Premature Granulocytic Development in Zebrafish." International Journal of Molecular Sciences 23, no. 7 (2022): 3833. http://dx.doi.org/10.3390/ijms23073833.

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Gene expression is tightly regulated during hematopoiesis. Recent studies have suggested that RNA polymerase II (Pol II) promoter proximal pausing, a temporary stalling downstream of the promoter region after initiation, plays a critical role in regulating the expression of various genes in metazoans. However, the function of proximal pausing in hematopoietic gene regulation remains largely unknown. The negative elongation factor (NELF) complex is a key factor important for this proximal pausing. Previous studies have suggested that NELF regulates granulocytic differentiation in vitro, but its

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2

Yamaguchi, Yuki, Naoto Inukai, Takashi Narita, Tadashi Wada, and Hiroshi Handa. "Evidence that Negative Elongation Factor Represses Transcription Elongation through Binding to a DRB Sensitivity-Inducing Factor/RNA Polymerase II Complex and RNA." Molecular and Cellular Biology 22, no. 9 (2002): 2918–27. http://dx.doi.org/10.1128/mcb.22.9.2918-2927.2002.

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ABSTRACT Negative elongation factor (NELF) is a human transcription factor complex that cooperates with DRB sensitivity-inducing factor (DSIF)/hSpt4-hSpt5 to repress elongation by RNA polymerase II (RNAPII). NELF activity is associated with five polypeptides, including NELF-A, a candidate gene product for Wolf-Hirschhorn syndrome, and NELF-E, a putative RNA-binding protein with arginine-aspartic acid (RD) dipeptide repeats. Here we report several important findings regarding the DSIF/NELF-dependent elongation control. First, we have established an effective method for purifying the active NELF

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3

Missra, A., and D. S. Gilmour. "Interactions between DSIF (DRB sensitivity inducing factor), NELF (negative elongation factor), and the Drosophila RNA polymerase II transcription elongation complex." Proceedings of the National Academy of Sciences 107, no. 25 (2010): 11301–6. http://dx.doi.org/10.1073/pnas.1000681107.

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4

Yu, Li, Bin Zhang, Dinesh Deochand, et al. "Negative elongation factor complex enables macrophage inflammatory responses by controlling anti-inflammatory gene expression." Journal of Immunology 204, no. 1_Supplement (2020): 152.28. http://dx.doi.org/10.4049/jimmunol.204.supp.152.28.

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Abstract Studies on macrophage gene expression have historically focused on events leading to RNA polymerase II recruitment and transcription initiation whereas the contribution of post-initiation steps to macrophage activation remains poorly understood. Here, we report widespread promoter-proximal RNA polymerase II pausing in resting macrophages, marked by broad co-localization of the negative elongation factor (NELF) complex and facilitated by PU.1. Upon inflammatory stimulation, over 60% of activated transcriptome is regulated by polymerase pause-release and a transient genome-wide NELF dis

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5

Ruiz, Brittany Natalie, Alvaro Lucci, Anna Barry, Kai Zhang, and Hien Dang. "Abstract 1492: Interaction between Argonaute-2 and Negative Elongation Factor-E in hepatocellular carcinoma." Cancer Research 83, no. 7_Supplement (2023): 1492. http://dx.doi.org/10.1158/1538-7445.am2023-1492.

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Abstract Hepatocellular carcinoma (HCC) continues to be one of the leading cause of cancer-related deaths globally, whose incidence is on the rise in the United States. We and others have shown that high levels of AGO2 is associated with a worse prognosis in HCC patients. Specifically, we showed AGO2 promotes HCC progression by modulating MYC mRNA stability in an RNAi-independent manner. In addition to its canonical role as an RNA binding protein, AGO2 has been demonstrated to regulate gene expression by affecting RNA polymerase II (Pol II) pausing through the Negative Elongation Factor (NELF)

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6

Jadlowsky, Julie K., Masanori Nojima, Takashi Okamoto, and Koh Fujinaga. "Dominant negative mutant cyclin T1 proteins that inhibit HIV transcription by forming a kinase inactive complex with Tat." Journal of General Virology 89, no. 11 (2008): 2783–87. http://dx.doi.org/10.1099/vir.0.2008/002857-0.

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Transcription of the human immunodeficiency virus type 1 (HIV) requires the interaction of the cyclin T1 (CycT1) subunit of a host cellular factor, the positive transcription elongation factor b (P-TEFb), with the viral Tat protein, at the transactivation response element (TAR) of nascent transcripts. Because of this virus-specific interaction, CycT1 may potentially serve as a target for the development of anti-HIV therapies. Here we report the development of a mutant CycT1 protein, containing three threonine-to-alanine substitutions in the linker region between two of the cyclin boxes, which

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7

Zhang, Zhiqiang, Alicia Klatt, David S. Gilmour, and Andrew J. Henderson. "Negative Elongation Factor NELF Represses Human Immunodeficiency Virus Transcription by Pausing the RNA Polymerase II Complex." Journal of Biological Chemistry 282, no. 23 (2007): 16981–88. http://dx.doi.org/10.1074/jbc.m610688200.

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8

Zhou, Meisheng, Keven Huang, Kyung-Jin Jung, et al. "Bromodomain Protein Brd4 Regulates Human Immunodeficiency Virus Transcription through Phosphorylation of CDK9 at Threonine 29." Journal of Virology 83, no. 2 (2008): 1036–44. http://dx.doi.org/10.1128/jvi.01316-08.

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ABSTRACT Positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 (CDK9) and cyclin T, is a global transcription factor for eukaryotic gene expression, as well as a key factor for human immunodeficiency virus (HIV) transcription elongation. P-TEFb phosphorylates the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II), facilitating the transition from nonprocessive to processive transcription elongation. Recently, the bromodomain protein Brd4 has been shown to interact with the low-molecular-weight, active P-TEFb complex and recru

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9

Fu, Junjiang, Ho-Geun Yoon, Jun Qin, and Jiemin Wong. "Regulation of P-TEFb Elongation Complex Activity by CDK9 Acetylation." Molecular and Cellular Biology 27, no. 13 (2007): 4641–51. http://dx.doi.org/10.1128/mcb.00857-06.

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ABSTRACT P-TEFb, comprised of CDK9 and a cyclin T subunit, is a global transcriptional elongation factor important for most RNA polymerase II (pol II) transcription. P-TEFb facilitates transcription elongation in part by phosphorylating Ser2 of the heptapeptide repeat of the carboxy-terminal domain (CTD) of the largest subunit of pol II. Previous studies have shown that P-TEFb is subjected to negative regulation by forming an inactive complex with 7SK small RNA and HEXIM1. In an effort to investigate the molecular mechanism by which corepressor N-CoR mediates transcription repression, we ident

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Abbas, Ata, Roshan Padmanabhan, Todd Romigh, and Charis Eng. "PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy." Human Molecular Genetics 28, no. 17 (2019): 2826–34. http://dx.doi.org/10.1093/hmg/ddz112.

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Abstract Control of gene expression is one of the most complex yet continuous physiological processes impacting cellular homeostasis. RNA polymerase II (Pol II) transcription is tightly regulated at promoter-proximal regions by intricate dynamic processes including Pol II pausing, release into elongation and premature termination. Pol II pausing is a phenomenon where Pol II complex pauses within 30–60 nucleotides after initiating the transcription. Negative elongation factor (NELF) and DRB sensitivity inducing factor (DSIF) contribute in the establishment of Pol II pausing, and positive transc

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11

Youssef, Aya, Heba Shawer, Alaa Afify, and Asma Amleh. "The potential involvement of the cofactor of BRCA1 in hepatocellular carcinoma pathogenesis." Advances in Modern Oncology Research 2, no. 4 (2016): 224. http://dx.doi.org/10.18282/amor.v2.i4.129.

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<p>The cofactor of BRCA1 (COBRA1), which also refers to negative elongation factor polypeptide B (NELF-B), is a negative elongation factor (NELF) subunit that has been implicated in the development and progression of several cancers. While reduced COBRA1 expression has been associated with metastatic breast cancer, COBRA1 negatively regulates the activator protein-1 (AP-1) complex, leading to the down-regulation of trefoil factor-1 (TFF1) expression in gastric cancer cell lines. The involvement of COBRA1 in hepatocellular carcinoma (HCC) tumor formation and progression is not known. Here

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Fujinaga, Koh, Dan Irwin, Matthias Geyer, and B. Matija Peterlin. "Optimized Chimeras between Kinase-Inactive Mutant Cdk9 and Truncated Cyclin T1 Proteins Efficiently Inhibit Tat Transactivation and Human Immunodeficiency Virus Gene Expression." Journal of Virology 76, no. 21 (2002): 10873–81. http://dx.doi.org/10.1128/jvi.76.21.10873-10881.2002.

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ABSTRACT The human cyclin T1 (hCycT1) protein from the positive transcription elongation factor b (P-TEFb) binds the transactivator Tat and the transactivation response (TAR) RNA stem loop from human immunodeficiency virus type 1 (HIV). This complex activates the elongation of viral transcription. To create effective inhibitors of Tat and thus HIV replication, we constructed mutant hCycT1 proteins that are defective in binding its kinase partner, Cdk9, or TAR. Although these mutant hCycT1 proteins did not increase Tat transactivation in murine cells, their dominant-negative effects were small

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13

Narita, Takashi, Yuki Yamaguchi, Keiichi Yano, et al. "Human Transcription Elongation Factor NELF: Identification of Novel Subunits and Reconstitution of the Functionally Active Complex." Molecular and Cellular Biology 23, no. 6 (2003): 1863–73. http://dx.doi.org/10.1128/mcb.23.6.1863-1873.2003.

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ABSTRACT The multisubunit transcription elongation factor NELF (for negative elongation factor) acts together with DRB (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF)/human Spt4-Spt5 to cause transcriptional pausing of RNA polymerase II (RNAPII). NELF activity is associated with five polypeptides, A to E. NELF-A has sequence similarity to hepatitis delta antigen (HDAg), the viral protein that binds to and activates RNAPII, whereas NELF-E is an RNA-binding protein whose RNA-binding activity is critical for NELF function. To understand the interactions of DSIF,

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14

Wenzel, Sabine, Berta M. Martins, Paul Rösch, and Birgitta M. Wöhrl. "Crystal structure of the human transcription elongation factor DSIF hSpt4 subunit in complex with the hSpt5 dimerization interface." Biochemical Journal 425, no. 2 (2009): 373–80. http://dx.doi.org/10.1042/bj20091422.

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The eukaryotic transcription elongation factor DSIF [DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidazole) sensitivity-inducing factor] is composed of two subunits, hSpt4 and hSpt5, which are homologous to the yeast factors Spt4 and Spt5. DSIF is involved in regulating the processivity of RNA polymerase II and plays an essential role in transcriptional activation of eukaryotes. At several eukaryotic promoters, DSIF, together with NELF (negative elongation factor), leads to promoter-proximal pausing of RNA polymerase II. In the present paper we describe the crystal structure of hSpt4 in complex w

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Chen, Zheng, Jing Ye, Usama Ashraf, et al. "MicroRNA-33a-5p Modulates Japanese Encephalitis Virus Replication by Targeting Eukaryotic Translation Elongation Factor 1A1." Journal of Virology 90, no. 7 (2016): 3722–34. http://dx.doi.org/10.1128/jvi.03242-15.

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ABSTRACTJapanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. However, the molecular mechanism for JEV pathogenesis is still unclear. MicroRNAs (miRNAs) are small noncoding RNAs that act as gene regulators. They are directly or indirectly involved in many cellular functions owing to their ability to target mRNAs for degradation or translational repression. However, how cellular miRNAs are regulated and their functions during JEV infection are largely unknown. In the present study, we found that JEV infection downre

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16

Hurtado-Guerrero, Ramon, Tal Zusman, Shalini Pathak, et al. "Molecular mechanism of elongation factor 1A inhibition by a Legionella pneumophila glycosyltransferase." Biochemical Journal 426, no. 3 (2010): 281–92. http://dx.doi.org/10.1042/bj20091351.

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Legionnaires' disease is caused by a lethal colonization of alveolar macrophages with the Gram-negative bacterium Legionella pneumophila. LpGT (L. pneumophila glucosyltransferase; also known as Lgt1) has recently been identified as a virulence factor, shutting down protein synthesis in the human cell by specific glucosylation of EF1A (elongation factor 1A), using an unknown mode of substrate recognition and a retaining mechanism for glycosyl transfer. We have determined the crystal structure of LpGT in complex with substrates, revealing a GT-A fold with two unusual protruding domains. Through

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Cisneros, William J., Shimaa H. A. Soliman, Miriam Walter, et al. "Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal." PLOS Pathogens 20, no. 9 (2024): e1012083. http://dx.doi.org/10.1371/journal.ppat.1012083.

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The persistence of HIV-1 in long-lived latent reservoirs during suppressive antiretroviral therapy (ART) remains one of the principal barriers to a functional cure. Blocks to transcriptional elongation play a central role in maintaining the latent state, and several latency reversal strategies focus on the release of positive transcription elongation factor b (P-TEFb) from sequestration by negative regulatory complexes, such as the 7SK complex and BRD4. Another major cellular reservoir of P-TEFb is in Super Elongation Complexes (SECs), which play broad regulatory roles in host gene expression.

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Jiang, Huimin, and B. Matija Peterlin. "Differential Chromatin Looping Regulates CD4 Expression in Immature Thymocytes." Molecular and Cellular Biology 28, no. 3 (2007): 907–12. http://dx.doi.org/10.1128/mcb.00909-07.

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ABSTRACT Runx1 binds the silencer and represses CD4 transcription in immature thymocytes. In this study, using looping chromatin immunoprecipitation and chromatin conformation capture assays, we demonstrated that interactions between Runx1 and positive elongation factor b (P-TEFb) appose the silencer and enhancer in CD4-negative thymoma cells and double-negative immature thymocytes. This chromatin loop decoys P-TEFb away from the promoter, thus preventing RNA polymerase II from elongating on the CD4 gene. In the absence of Runx1 on the silencer, P-TEFb interacts with the transcription complex,

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Moir, Robert D., Timothy P. Spann, Harald Herrmann, and Robert D. Goldman. "Disruption of Nuclear Lamin Organization Blocks the Elongation Phase of DNA Replication." Journal of Cell Biology 149, no. 6 (2000): 1179–92. http://dx.doi.org/10.1083/jcb.149.6.1179.

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The role of nuclear lamins in DNA replication is unclear. To address this, nuclei were assembled in Xenopus extracts containing AraC, a reversible inhibitor that blocks near the onset of the elongation phase of replication. Dominant-negative lamin mutants lacking their NH2-terminal domains were added to assembled nuclei to disrupt lamin organization. This prevented the resumption of DNA replication after the release of the AraC block. This inhibition of replication was not due to gross disruption of nuclear envelope structure and function. The organization of initiation factors was not altered

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Iankova, Irena, Rasmus K. Petersen, Jean-Sébastien Annicotte та ін. "Peroxisome Proliferator-Activated Receptor γ Recruits the Positive Transcription Elongation Factor b Complex to Activate Transcription and Promote Adipogenesis". Molecular Endocrinology 20, № 7 (2006): 1494–505. http://dx.doi.org/10.1210/me.2005-0222.

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Abstract Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9 in

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Nagarkar, Sanket, Ruchi Wasnik, Pravallika Govada, Stephen Cohen, and L. S. Shashidhara. "Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila." Genetics 216, no. 1 (2020): 67–77. http://dx.doi.org/10.1534/genetics.120.303419.

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Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression co

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Monge, I., R. Krishnamurthy, D. Sims, et al. "Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development." Development 128, no. 8 (2001): 1239–52. http://dx.doi.org/10.1242/dev.128.8.1239.

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We report loss- and gain-of-function analyses that identify essential roles in development for Drosophila transcription factor AP-2. A mutagenesis screen yielded 16 lethal point mutant alleles of dAP-2. Null mutants die as adults or late pupae with a reduced proboscis, severely shortened legs (~30% of normal length) lacking tarsal joints, and disruptions in the protocerebral central complex, a brain region critical for locomotion. Seven hypomorphic alleles constitute a phenotypic series yielding hemizygous adults with legs ranging from 40–95% of normal length. Hypomorphic alleles show additive

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Yan, Junpeng, Qing Li, Sam Lievens, Jan Tavernier, and Jianxin You. "Abrogation of the Brd4-Positive Transcription Elongation Factor b Complex by Papillomavirus E2 Protein Contributes to Viral Oncogene Repression." Journal of Virology 84, no. 1 (2009): 76–87. http://dx.doi.org/10.1128/jvi.01647-09.

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ABSTRACT The cellular bromodomain protein Brd4 is a major interacting partner of the papillomavirus (PV) E2 protein. Interaction of E2 with Brd4 contributes to viral episome maintenance. The E2-Brd4 interaction also plays an important role in repressing viral oncogene expression from the integrated viral genome in human PV (HPV)-positive cancer cells. However, the underlying mechanism is not clearly understood. In host cells, Brd4 recruits positive transcription elongation factor b (P-TEFb) to stimulate RNA polymerase II phosphorylation during cellular and viral gene expression. P-TEFb associa

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Mukherjee, Kaustav, James J. Bieker, and Venkata Srinivas Mohan Nimai Dangeti. "EKLF/Klf1 Regulates Erythroid Transcription By Its Pioneering Activity and Subsequent Control of RNA Pol II Pause-Release." Blood 138, Supplement 1 (2021): 283. http://dx.doi.org/10.1182/blood-2021-151470.

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Abstract EKLF/Klf1 is a master transcriptional activator of critical genes that regulate both erythroid fate specification and terminal erythroid maturation. EKLF binds to DNA using three Zn-fingers at its C-terminus while the N-terminus constitutes a transcription activation domain (TAD) that interacts with various transcription co-factors including the protein acetylase CBP. An autosomal semi-dominant mutation at a single residue (E339D) in the mouse EKLF Zn-finger leads to Neonatal anemia (Nan). A mutation at the same residue in human EKLF (E325K) causes Congenital Dyserythropoietic Anemia

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Lamm, Ryan, Anna Barry-Wolbers, Kai Zhang, Keyur Patel, and Hien T. Dang. "Abstract 508: Clinical significance of a negative elongation factor-E (NELF-E) single nucleotide polymorphism in hepatocellular carcinoma (HCC)." Cancer Research 82, no. 12_Supplement (2022): 508. http://dx.doi.org/10.1158/1538-7445.am2022-508.

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Abstract Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide. Multiple causative etiologies, such as hepatitis B and C (HBV/HCV), alcohol, and non-alcoholic steatohepatitis (NASH), lead to heterogeneous tumor microenvironments and modest at best responses to available therapy. Previous work has identified that high levels of negative elongation factor-E (NELF-E), part of the transcription regulating NELF complex, promote tumor progression and significantly lower overall survival in more than 38% of HCC tumors. Further studies identified a germline single nu

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Orynbekov, D. R., Zh Kalibekkyzy, A. N. Nurgazezova, G. N. Nurymkhan, Wu Gang, and M. Muratkhan. "DEVELOPMENT AND RSM-BASED OPTIMIZATION OF BIODEGRADABLE EDIBLE FILMS FROM ELECTRON BEAM-IRRADIATED STARCH AND CHITOSAN." Bulletin of Shakarim University. Technical Sciences, no. 2(18) (July 8, 2025): 336–45. https://doi.org/10.53360/2788-7995-2025-2(18)-41.

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This study aimed to develop and optimize edible antimicrobial films using electron beam-irradiated starches and biopolymer additives. Rice starch (“Marzhan” variety) and cassava starch (“Cassava 531” variety) were physically modified via irradiation at doses of 0, 3, 6, and 9 kGy using an ILU-10 accelerator. Film-forming solutions were prepared by blending starch, chitosan, and glycerol, followed by casting and drying. One-Factor-at-a-Time (OFAT) screening was conducted to evaluate the effects of starch content, gelatinization time, glycerol, and chitosan on film properties including tensile s

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Liu, Gang, Wayne M. Grant, Daniel Persky, Vaughan M. Latham, Robert H. Singer та John Condeelis. "Interactions of Elongation Factor 1α with F-Actin and β-Actin mRNA: Implications for Anchoring mRNA in Cell Protrusions". Molecular Biology of the Cell 13, № 2 (2002): 579–92. http://dx.doi.org/10.1091/mbc.01-03-0140.

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The targeting of mRNA and local protein synthesis is important for the generation and maintenance of cell polarity. As part of the translational machinery as well as an actin/microtubule-binding protein, elongation factor 1α (EF1α) is a candidate linker between the protein translation apparatus and the cytoskeleton. We demonstrate in this work that EF1α colocalizes with β-actin mRNA and F-actin in protrusions of chicken embryo fibroblasts and binds directly to F-actin and β-actin mRNA simultaneously in vitro in actin cosedimentation and enzyme-linked immunosorbent assays. To investigate the ro

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Zhou, Danlei, Michalea Lai, Aiqin Luo, and Chack-Yung Yu. "An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex." Cells 8, no. 9 (2019): 1008. http://dx.doi.org/10.3390/cells8091008.

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At the central region of the mammalian major histocompatibility complex (MHC) is a complement gene cluster that codes for constituents of complement C3 convertases (C2, factor B and C4). Complement activation drives the humoral effector functions for immune response. Sandwiched between the genes for serine proteinase factor B and anchor protein C4 are four less known but critically important genes coding for essential functions related to metabolism and surveillance of RNA during the transcriptional and translational processes of gene expression. These four genes are NELF-E (RD), SKIV2L (SKI2W

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Gibson, Bryan A., Yajie Zhang, Hong Jiang, et al. "Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation." Science 353, no. 6294 (2016): 45–50. http://dx.doi.org/10.1126/science.aaf7865.

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Poly[adenosine diphosphate (ADP)–ribose] polymerases (PARPs) are a family of enzymes that modulate diverse biological processes through covalent transfer of ADP-ribose from the oxidized form of nicotinamide adenine dinucleotide (NAD+) onto substrate proteins. Here we report a robust NAD+ analog–sensitive approach for PARPs, which allows PARP-specific ADP-ribosylation of substrates that is suitable for subsequent copper-catalyzed azide-alkyne cycloaddition reactions. Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousa

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Reynolds, Laura, Ryan Lamm, Anna Barry, Meghan Grim, Kai Zhang, and Hien Dang. "Abstract 1490: Exon exclusion of NELF-E produces an anti-tumorigenic truncated isoform in hepatocellular carcinoma." Cancer Research 83, no. 7_Supplement (2023): 1490. http://dx.doi.org/10.1158/1538-7445.am2023-1490.

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Abstract Overexpression of negative elongation factor E (NELF-E), a subunit of the negative elongation factor (NELF) complex involved in transcription pausing, has been implicated in poor hepatocellular carcinoma (HCC) outcome. We recently discovered an intronic heterozygous single nucleotide polymorphism (SNP), rs79208225 (G&gt;A), near a spliceosome binding site in less than 1% of the general population but ~4% of our HCC cohort. HCC patients with the SNP had significantly longer times till recurrence (p=0.001) and better overall survival (p=0.02) compared to patients without the SNP. Us

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Wolf, Dieter A., Yingying Lin, Haoran Duan, and Yabin Cheng. "eIF-Three to Tango: emerging functions of translation initiation factor eIF3 in protein synthesis and disease." Journal of Molecular Cell Biology 12, no. 6 (2020): 403–9. http://dx.doi.org/10.1093/jmcb/mjaa018.

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Abstract Studies over the past three years have substantially expanded the involvements of eukaryotic initiation factor 3 (eIF3) in messenger RNA (mRNA) translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination, and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting

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Alberio, Tiziana, Mariam Shallak, Amruth Kaleem Basha Shaik, Roberto Sergio Accolla, and Greta Forlani. "A Truncated Isoform of Cyclin T1 Could Contribute to the Non-Permissive HIV-1 Phenotype of U937 Promonocytic Cells." Viruses 16, no. 8 (2024): 1176. http://dx.doi.org/10.3390/v16081176.

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The different susceptibility to HIV-1 infection in U937 cells—permissive (Plus) or nonpermissive (Minus)—is linked to the expression in Minus cells of interferon (IFN)-γ inducible antiviral factors such as tripartite motif-containing protein 22 (TRIM22) and class II transactivator (CIITA). CIITA interacts with Cyclin T1, a key component of the Positive-Transcription Elongation Factor b (P-TEFb) complex needed for the efficient transcription of HIV-1 upon interaction with the viral transactivator Tat. TRIM22 interacts with CIITA, recruiting it into nuclear bodies together with Cyclin T1. A 50 k

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Connolly, Eileen, Steve Braunstein, Silvia Formenti, and Robert J. Schneider. "Hypoxia Inhibits Protein Synthesis through a 4E-BP1 and Elongation Factor 2 Kinase Pathway Controlled by mTOR and Uncoupled in Breast Cancer Cells." Molecular and Cellular Biology 26, no. 10 (2006): 3955–65. http://dx.doi.org/10.1128/mcb.26.10.3955-3965.2006.

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ABSTRACT Hypoxia is a state of low oxygen availability that limits tumor growth. The mechanism of protein synthesis inhibition by hypoxia and its circumvention by transformation are not well understood. Hypoxic breast epithelial cells are shown to downregulate protein synthesis by inhibition of the kinase mTOR, which suppresses mRNA translation through a novel mechanism mitigated in transformed cells: disruption of proteasome-targeted degradation of eukaryotic elongation factor 2 (eEF2) kinase and activation of the regulatory protein 4E-BP1. In transformed breast epithelial cells under hypoxia

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Chávez, Sebastián, Marı́a Garcı́a-Rubio, Félix Prado, and Andrés Aguilera. "Hpr1 Is Preferentially Required for Transcription of Either Long or G+C-Rich DNA Sequences in Saccharomyces cerevisiae." Molecular and Cellular Biology 21, no. 20 (2001): 7054–64. http://dx.doi.org/10.1128/mcb.21.20.7054-7064.2001.

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ABSTRACT Hpr1 forms, together with Tho2, Mft1, and Thp2, the THO complex, which controls transcription elongation and genome stability inSaccharomyces cerevisiae. Mutations in genes encoding the THO complex confer strong transcription-impairment and hyperrecombination phenotypes in the bacterial lacZgene. In this work we demonstrate that Hpr1 is a factor required for transcription of long as well as G+C-rich DNA sequences. Using different lacZ segments fused to the GAL1promoter, we show that the negative effect of lacZsequences on transcription depends on their distance from the promoter. In p

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Guiro, Joana, Mathias Fagbemi, Michael Tellier, et al. "CAPTURE of the Human U2 snRNA Genes Expands the Repertoire of Associated Factors." Biomolecules 12, no. 5 (2022): 704. http://dx.doi.org/10.3390/biom12050704.

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In order to identify factors involved in transcription of human snRNA genes and 3′ end processing of the transcripts, we have carried out CRISPR affinity purification in situ of regulatory elements (CAPTURE), which is deadCas9-mediated pull-down, of the tandemly repeated U2 snRNA genes in human cells. CAPTURE enriched many factors expected to be associated with these human snRNA genes including RNA polymerase II (pol II), Cyclin-Dependent Kinase 7 (CDK7), Negative Elongation Factor (NELF), Suppressor of Ty 5 (SPT5), Mediator 23 (MED23) and several subunits of the Integrator Complex. Suppressor

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Braun, Molly R., Sarah L. Noton, Emmeline L. Blanchard, et al. "Respiratory syncytial virus M2-1 protein associates non-specifically with viral messenger RNA and with specific cellular messenger RNA transcripts." PLOS Pathogens 17, no. 5 (2021): e1009589. http://dx.doi.org/10.1371/journal.ppat.1009589.

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Respiratory syncytial virus (RSV) is a major cause of respiratory disease in infants and the elderly. RSV is a non-segmented negative strand RNA virus. The viral M2-1 protein plays a key role in viral transcription, serving as an elongation factor to enable synthesis of full-length mRNAs. M2-1 contains an unusual CCCH zinc-finger motif that is conserved in the related human metapneumovirus M2-1 protein and filovirus VP30 proteins. Previous biochemical studies have suggested that RSV M2-1 might bind to specific virus RNA sequences, such as the transcription gene end signals or poly A tails, but

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Parent, Marianne, Tetsu M. C. Yung, Ann Rancourt, et al. "Poly(ADP-ribose) Polymerase-1 Is a Negative Regulator of HIV-1 Transcription through Competitive Binding to TAR RNA with Tat·Positive Transcription Elongation Factor b (p-TEFb) Complex." Journal of Biological Chemistry 280, no. 1 (2004): 448–57. http://dx.doi.org/10.1074/jbc.m408435200.

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Hagkarim, Nafiseh Chalabi, Morteza Chalabi Hajkarim, Toru Suzuki, et al. "Disruption of the Mammalian Ccr4–Not Complex Contributes to Transcription-Mediated Genome Instability." Cells 12, no. 14 (2023): 1868. http://dx.doi.org/10.3390/cells12141868.

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The mammalian Ccr4–Not complex, carbon catabolite repression 4 (Ccr4)-negative on TATA-less (Not), is a large, highly conserved, multifunctional assembly of proteins that acts at different cellular levels to regulate gene expression. It is involved in the control of the cell cycle, chromatin modification, activation and inhibition of transcription initiation, control of transcription elongation, RNA export, and nuclear RNA surveillance; the Ccr4–Not complex also plays a central role in the regulation of mRNA decay. Growing evidence suggests that gene transcription has a vital role in shaping t

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Szojka, Zsófia Ilona, Balázs Kunkli, Irene Wanjiru Kiarie, et al. "Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx." International Journal of Molecular Sciences 26, no. 8 (2025): 3460. https://doi.org/10.3390/ijms26083460.

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Viral protein X (Vpx) is a unique accessory protein encoded by the genome of the human immunodeficiency virus type 2 (HIV-2) and lineages of the simian immunodeficiency virus of sooty mangabeys. So far, counteracting the cellular restriction factor SAMHD1 and mediating the efficient translocation of viral pre-integration complex have been recognized as key functions of Vpx; however, a thorough exploration of its effects on the cellular transcriptome and cytokine milieu has not yet been undertaken. In this study, we carried out the transcriptomic analysis of THP-1 cells and determined different

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Song, Qingxin, Atsumi Ando, Dongqing Xu, et al. "Diurnal down-regulation of ethylene biosynthesis mediates biomass heterosis." Proceedings of the National Academy of Sciences 115, no. 21 (2018): 5606–11. http://dx.doi.org/10.1073/pnas.1722068115.

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Heterosis is widely applied in agriculture; however, the underlying molecular mechanisms for superior performance are not well understood. Ethylene biosynthesis and signaling genes are shown to be down-regulated in Arabidopsis interspecific hybrids. Ethylene is a plant hormone that promotes fruit ripening and maturation but inhibits hypocotyl elongation. Here we report that application of exogenous ethylene could eliminate biomass vigor in Arabidopsis thaliana F1 hybrids, suggesting a negative role of ethylene in heterosis. Ethylene biosynthesis is mediated by the rate-limiting enzyme, 1-amino

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Bender, Kyle W., Daniel Couto, Yasuhiro Kadota, et al. "Activation loop phosphorylaton of a non-RD receptor kinase initiates plant innate immune signaling." Proceedings of the National Academy of Sciences 118, no. 38 (2021): e2108242118. http://dx.doi.org/10.1073/pnas.2108242118.

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Receptor kinases (RKs) are fundamental for extracellular sensing and regulate development and stress responses across kingdoms. In plants, leucine-rich repeat receptor kinases (LRR-RKs) are primarily peptide receptors that regulate responses to myriad internal and external stimuli. Phosphorylation of LRR-RK cytoplasmic domains is among the earliest responses following ligand perception, and reciprocal transphosphorylation between a receptor and its coreceptor is thought to activate the receptor complex. Originally proposed based on characterization of the brassinosteroid receptor, the prevalen

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Lashkevich, Kseniya A., Valeriya I. Shlyk, Artem S. Kushchenko, Vadim N. Gladyshev, Elena Z. Alkalaeva, and Sergey E. Dmitriev. "CTELS: A Cell-Free System for the Analysis of Translation Termination Rate." Biomolecules 10, no. 6 (2020): 911. http://dx.doi.org/10.3390/biom10060911.

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Translation termination is the final step in protein biosynthesis when the synthesized polypeptide is released from the ribosome. Understanding this complex process is important for treatment of many human disorders caused by nonsense mutations in important genes. Here, we present a new method for the analysis of translation termination rate in cell-free systems, CTELS (for C-terminally extended luciferase-based system). This approach was based on a continuously measured luciferase activity during in vitro translation reaction of two reporter mRNA, one of which encodes a C-terminally extended

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Spann, Timothy P., Robert D. Moir, Anne E. Goldman, Reimer Stick, and Robert D. Goldman. "Disruption of Nuclear Lamin Organization Alters the Distribution of Replication Factors and Inhibits DNA Synthesis." Journal of Cell Biology 136, no. 6 (1997): 1201–12. http://dx.doi.org/10.1083/jcb.136.6.1201.

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The nuclear lamina is a fibrous structure that lies at the interface between the nuclear envelope and the nucleoplasm. The major proteins comprising the lamina, the nuclear lamins, are also found in foci in the nucleoplasm, distinct from the peripheral lamina. The nuclear lamins have been associated with a number of processes in the nucleus, including DNA replication. To further characterize the specific role of lamins in DNA replication, we have used a truncated human lamin as a dominant negative mutant to perturb lamin organization. This protein disrupts the lamin organization of nuclei when

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Cruz-Gordillo, Peter, Megan E. Honeywell, Nicholas W. Harper, Thomas Leete, and Michael J. Lee. "ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells." Science Signaling 13, no. 658 (2020): eabb9820. http://dx.doi.org/10.1126/scisignal.abb9820.

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Targeted therapeutics for cancer generally exploit “oncogene addiction,” a phenomenon in which the growth and survival of tumor cells depend on the activity of a particular protein. However, the efficacy of oncogene-targeted therapies varies substantially. For instance, targeting epidermal growth factor receptor (EGFR) signaling is effective in some non–small cell lung cancer (NSCLC) but not in triple-negative breast cancer (TNBC), although these cancers show a similar degree of increase in EGFR activity. Using a genome-wide CRISPR-Cas9 genetic knockout screen, we found that the Elongator (ELP

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İnalkac Gemici, Yagmur, Irem Tasci, Muhammed Dundar, et al. "Epigenetic analysis of heat shock activator complex in the peripheral blood of Parkinson's disease patients and its clinical significance." Turkish Journal of Neurology 30, no. 2 (2024): 76–85. http://dx.doi.org/10.55697/tnd.2024.110.

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Objectives: This study aimed to investigate the methylation changes of related genes in the peripheral blood and their clinical significance in Parkinson's disease (PD) and whether the methylation change of the gene encoding long noncoding RNA was different in the blood of patients and controls. Patients and methods: This prospective cross-sectional, controlled study was conducted with 45 participants (22 males, 23 females; mean age: 60.7±5.9 years; range, 53 to 75 years) between June 2020 and June 2021. Drug-naive patients diagnosed with PD were included in this study. Those with PD and a Min

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Hung, Wesley J., Rachel S. Roberson, Jaime Taft, and Daniel Y. Wu. "Human BAG-1 Proteins Bind to the Cellular Stress Response Protein GADD34 and Interfere with GADD34 Functions." Molecular and Cellular Biology 23, no. 10 (2003): 3477–86. http://dx.doi.org/10.1128/mcb.23.10.3477-3486.2003.

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ABSTRACT The cellular stress response protein GADD34 mediates growth arrest and apoptosis in response to DNA damage, negative growth signals, and protein malfolding. GADD34 binds to protein phosphatase PP1 and can attenuate the translational elongation of key transcriptional factors through dephosphorylation of eukaryotic initiation factor 2α (eIF2α). Recently, we reported the involvement of human SNF5/INI1 (hSNF5/INI1) protein in the functions of GADD34 and showed that hSNF5/INI1 binds GADD34 and stimulates the bound PP1 phosphatase activity. To better understand the regulatory and functional

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Łyżeń, Robert, Grzegorz Wȩgrzyn, Alicja Wȩgrzyn та Agnieszka Szalewska-Pałasz. "Stimulation of the λ p R promoter by Escherichia coli SeqA protein requires downstream GATC sequences and involves late stages of transcription initiation". Microbiology 152, № 10 (2006): 2985–92. http://dx.doi.org/10.1099/mic.0.29110-0.

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Escherichia coli SeqA protein is a major negative regulator of chromosomal DNA replication acting by sequestration, and thus inactivation, of newly formed oriC regions. However, other activities of this protein have been discovered recently, one of which is regulation of transcription. SeqA has been demonstrated to be a specific transcription factor acting at bacteriophage λ promoters p I, p aQ and p R. While SeqA-mediated stimulation of p I and p aQ occurs by facilitating functions of another transcription activator protein, cII, a mechanism for stimulation of p R remains largely unknown. Her

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Azcona, F., M. Sole, J. Dorado, P. Ross, E. Terán, and S. Demyda-Peyrás. "155 Whole genome association analysis suggests an influence of inbreeding on bull sperm morphometry." Reproduction, Fertility and Development 31, no. 1 (2019): 202. http://dx.doi.org/10.1071/rdv31n1ab155.

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Inbreeding depression, the genetic condition caused by mating related individuals, is particularly important in several cattle breeds with limited effective populations. This condition is often associated with decreases in performance, including fertility. Furthermore, sperm head morphometry was associated with fertility in several species. To our knowledge, the influence of inbreeding on sperm morphometry has not been widely reported in cattle. In this study, a Sperm Class Analyzer (SCA™, Microptic S.L., Barcelona, Spain) was used to characterise 7 sperm morphometry parameters in 59 Retinta b

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Mameli, Giuseppe, Satish L. Deshmane, Mohammad Ghafouri та ін. "C/EBPβ regulates human immunodeficiency virus 1 gene expression through its association with cdk9". Journal of General Virology 88, № 2 (2007): 631–40. http://dx.doi.org/10.1099/vir.0.82487-0.

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Transcriptional regulation of the human immunodeficiency virus type 1 (HIV-1) is a complex event that requires the cooperative action of both viral (e.g. Tat) and cellular (e.g. C/EBPβ, NF-κB) factors. The HIV-1 Tat protein recruits the human positive transcription elongation factor P-TEFb, consisting of cdk9 and cyclin T1, to the HIV-1 transactivation response (TAR) region. In the absence of TAR, Tat activates the HIV-1 long terminal repeat (LTR) through its association with several cellular factors including C/EBPβ. C/EBPβ is a member of the CCAAT/enhancer-binding protein family of transcrip

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Ioannou, Ioanna, Angeliki Chatziantoniou, Constantinos Drenios, Panayiota Christodoulou, Malamati Kourti, and Apostolos Zaravinos. "Signatures of Co-Deregulated Genes and Their Transcriptional Regulators in Kidney Cancers." International Journal of Molecular Sciences 24, no. 7 (2023): 6577. http://dx.doi.org/10.3390/ijms24076577.

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There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we reanalyzed 10 Gene Expression Omnibus (GEO) studies to detect and annotate co-deregulated signatures across different subtypes of kidney cancer or in single-gene perturbation experiments in kidney cancer cells and/or tissue. Using a systems biology approach, we aimed to decipher the networks they f

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