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Query: UNIPROT:P23193 (transcription elongation factor)
 739 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The products of the yeast CDC73 and PAF1 genes were originally identified as RNA polymerase II-associated proteins. Paf1p is a nuclear protein important for cell growth and transcriptional regulation of a subset of yeast genes. In this study we demonstrate that the product of CDC73 is a nuclear protein that interacts directly with purified RNA polymerase II in vitro. Deletion of CDC73 confers a temperature-sensitive phenotype. Combination of the cdc73 mutation with the more severe paf1 mutation does not result in an enhanced phenotype, indicating that the two proteins may function in the same cellular processes. To determine the relationship between Cdc73p and Paf1p and the recently described holoenzyme form of RNA polymerase II, we created yeast strains containing glutathione S-transferase (GST)-tagged forms of CDC73, PAF1, and TFG2 functionally replacing the chromosomal copies of the genes. Isolation of GST-tagged Cdc73p and Paf1p complexes has revealed a unique form of RNA polymerase II that contains both Cdc73p and Paf1p but lacks the Srbps found in the holoenzyme. The Cdc73p-Paf1p-RNA polymerase II-containing complex also includes Gal11p, and the general initiation factors TFIIB and TFIIF, but lacks TBP, TFIIH, and transcription elongation factor TFIIS as well as the Srbps. The Srbp-containing holoenzyme does not include either Paf1p or Cdc73p, demonstrating that these two forms of RNA polymerase II are distinct. In confirmation of the hypothesis that the two forms coexist in yeast cells, we found that a TFIIF-containing complex isolated via the GST-tagged Tfg2p construct contains both (i) the Srbps and (ii) Cdc73p and Paf1p. The Srbps and Cdc73p-Paf1p therefore appear to define two complexes with partially redundant, essential functions in the yeast cell. Using the technique of differential display, we have identified several genes whose transcripts require Cdc73p and/or Paf1p for normal levels of expression. Our analysis suggests that there are multiple RNA polymerase II-containing complexes involved in the expression of different classes of protein-coding genes.
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PMID:Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex distinct from the Srbp-containing holoenzyme. 903 43

Human immunodeficiency virus, type 1 (HIV-1) Tat protein activates transcription from the HIV-1 long terminal repeat. Tat interacts with TFIIH and Tat-associated kinase (a transcription elongation factor P-TEFb) and requires the carboxyl-terminal domain of the largest subunit of RNA polymerase II (pol II) for transactivation. We developed a stepwise RNA pol II walking approach and used Western blotting to determine the role of TFIIH and P-TEFb in HIV-1 transcription elongation. Our results demonstrate the new findings that P-TEFb is a component of the preinitiation complex and travels with the elongating RNA pol II, whereas TFIIH is released from the elongation complexes before the trans-activation responsive region RNA is synthesized. Our results suggest that TFIIH and P-TEFb are involved in the clearance of promoter-proximal pausing of RNA pol II on the HIV-1 long terminal repeat at different stages.
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PMID:Tat-associated kinase (P-TEFb): a component of transcription preinitiation and elongation complexes. 1006 4

Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of Cdk9 and cyclin T1, to the HIV-1 promoter via cooperative binding to the nascent HIV-1 transactivation response RNA element. The Cdk9 kinase activity has been shown to be essential for P-TEFb to hyperphosphorylate the carboxy-terminal domain (CTD) of RNA polymerase II and mediate Tat transactivation. Recent reports have shown that Tat can also interact with the multisubunit transcription factor TFIIH complex and increase the phosphorylation of CTD by the Cdk-activating kinase (CAK) complex associated with the core TFIIH. These observations have led to the proposal that TFIIH and P-TEFb may act sequentially and in a concerted manner to promote phosphorylation of CTD and increase polymerase processivity. Here, we show that under conditions in which a specific and efficient interaction between Tat and P-TEFb is observed, only a weak interaction between Tat and TFIIH that is independent of critical amino acid residues in the Tat transactivation domain can be detected. Furthermore, immunodepletion of CAK under high-salt conditions, which allow CAK to be dissociated from core-TFIIH, has no effect on either basal HIV-1 transcription or Tat activation of polymerase elongation in vitro. Therefore, unlike the P-TEFb kinase activity that is essential for Tat activation of HIV-1 transcriptional elongation, the CAK kinase associated with TFIIH appears to be dispensable for Tat function.
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PMID:Tat activates human immunodeficiency virus type 1 transcriptional elongation independent of TFIIH kinase. 1008 52

Eukaryotic mRNA synthesis is catalyzed by multisubunit RNA polymerase II and proceeds through multiple stages referred to as preinitiation, initiation, elongation, and termination. Over the past 20 years, biochemical studies of eukaryotic mRNA synthesis have largely focused on the preinitiation and initiation stages of transcription. These studies led to the discovery of the class of general initiation factors (TFIIB, TFIID, TFIIE, TFIIF, and TFIIH), which function in intimate association with RNA polymerase II and are required for selective binding of polymerase to its promoters, formation of the open complex, and synthesis of the first few phosphodiester bonds of nascent transcripts. Recently, biochemical studies of the elongation stage of eukaryotic mRNA synthesis have led to the discovery of several cellular proteins that have properties expected of general elongation factors and that have been found to play unanticipated roles in human disease. Among these candidate general elongation factors are the positive transcription elongation factor b (P-TEFb), eleven-nineteen lysine-rich in leukemia (ELL), Cockayne syndrome complementation group B (CSB), and elongin proteins, which all function in vitro to expedite elongation by RNA polymerase II by suppressing transient pausing or premature arrest by polymerase through direct interactions with the elongation complex. Despite their similar activities in elongation, the P-TEFb, ELL, CSB, and elongin proteins appear to play roles in a diverse collection of human diseases, including human immunodeficiency virus-1 infection, acute myeloid leukemia, Cockayne syndrome, and the familial cancer predisposition syndrome von Hippel-Lindau disease. here we review our current understanding of the P-TEFb, ELL, CSB, and elongin proteins, their mechanisms of action, and their roles in human disease.
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PMID:Transcription elongation and human disease. 1087 52

We report that the chromatin-specific transcription elongation factor FACT functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and NELF (negative elongation factor). We find that the kinase activity of TFIIH is dispensable for this activity, demonstrating that TFIIH-mediated CTD phosphorylation is not involved in the regulation of FACT and DSIF/NELF activities. Thus, we propose a novel transcriptional regulatory network in which DSIF/NELF inhibition of transcription is prevented by P-TEFb in cooperation with FACT. This study uncovers a novel role for FACT in the regulation of transcription on naked DNA that is independent of its activities on chromatin templates. In addition, this study reveals functional differences between P-TEFb and TFIIH in the regulation of transcription.
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PMID:FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. 1091 1

Tat stimulates human immunodeficiency virus, type 1 (HIV-1), transcription elongation by recruitment of the human transcription elongation factor P-TEFb, consisting of CDK9 and cyclin T1, to the TAR RNA structure. It has been demonstrated further that CDK9 phosphorylation is required for high affinity binding of Tat/P-TEFb to the TAR RNA structure and that the state of P-TEFb phosphorylation may regulate Tat transactivation. We now demonstrate that CDK9 phosphorylation is uniquely regulated in the HIV-1 preinitiation and elongation complexes. The presence of TFIIH in the HIV-1 preinitiation complex inhibits CDK9 phosphorylation. As TFIIH is released from the elongation complex between +14 and +36, CDK9 phosphorylation is observed. In contrast to the activity in the "soluble" complex, phosphorylation of CDK9 is increased by the presence of Tat in the transcription complexes. Consistent with these observations, we have demonstrated that purified TFIIH directly inhibits CDK9 autophosphorylation. By using recombinant TFIIH subcomplexes, our results suggest that the XPB subunit of TFIIH is responsible for this inhibition of CDK9 phosphorylation. Interestingly, our results further suggest that the phosphorylated form of CDK9 is the active kinase for RNA polymerase II carboxyl-terminal domain phosphorylation.
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PMID:TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1 transcription. 1157 68

AR may communicate with the general transcription machinery on the core promoter to exert its function as a transcriptional modulator. Our previous reports demonstrated that AR interacted with TFIIH and positive transcription elongation factor b (P-TEFb), and that phosphorylation of the carboxy-terminal domain in the largest subunit of RNA polymerase II might play important roles in AR-mediated transcription. These results suggest that AR may modulate gene expression by enhancing the efficiency of transcriptional elongation. Here we further demonstrate that co-expression of the second largest subunit of RNA polymerase II (RPB2) enhances AR transactivation. However, co-expression of the other subunits of RNA polymerase II or TFIIB did not show preferential enhancement of AR-mediated transcription. Furthermore, co-transfection of RPB2 with ER showed little effect on enhancement of ER transactivation. Together, AR may be able to interact with TFIIH, P-TEFb, and RPB2 to enhance transcription from AR target genes, such as prostate specific antigen that may play important roles in the prostate cancer progression.
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PMID:The second largest subunit of RNA polymerase II interacts with and enhances transactivation of androgen receptor. 1259 64

The androgen-androgen receptor (AR) signaling pathway plays a key role in proper development and function of male reproductive organs. Like other transcriptional regulators, AR may communicate with the general transcription machinery on the core promoter to exert its function as a transcriptional modulator. The molecular communication between AR and the general transcription machinery may be achieved either by the direct protein-protein interaction between AR and the general transcription machinery or by the indirect interaction mediated by coregulators. Analyses of AR-mediated transcription suggest that the orchestrated interaction of AR with the transcription factors IIF (TFIIF) and IIH (TFIIH), and positive transcription elongation factor b (P-TEFb), may increase efficiency of transcriptional elongation from the androgen target genes, such as prostate specific antigen (PSA). Based on studies so far, AR may regulate transcription not by enhanced assembly of preinitiation transcription complex but by regulating promoter clearance and elongation stage of transcription.
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PMID:Molecular communication between androgen receptor and general transcription machinery. 1264 23

Cyclin-dependent kinases (CDKs) are subunits of transcription factor (TF) IIH and positive transcription elongation factor b (P-TEFb). To define their functions, we mutated the TFIIH-associated kinase Mcs6 and P-TEFb homologs Cdk9 and Lsk1 of fission yeast, making them sensitive to inhibition by bulky purine analogs. Selective inhibition of Mcs6 or Cdk9 blocks cell division, alters RNA polymerase (Pol) II carboxyl-terminal domain (CTD) phosphorylation, and represses specific, overlapping subsets of transcripts. At a common target gene, both CDKs must be active for normal Pol II occupancy, and Spt5-a CDK substrate and regulator of elongation-accumulates disproportionately to Pol II when either kinase is inhibited. In contrast, Mcs6 activity is sufficient-and necessary-to recruit the Cdk9/Pcm1 (mRNA cap methyltransferase) complex. In vitro, phosphorylation of the CTD by Mcs6 stimulates subsequent phosphorylation by Cdk9. We propose that TFIIH primes the CTD and promotes recruitment of P-TEFb/Pcm1, serving to couple elongation and capping of select pre-mRNAs.
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PMID:TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. 1932 67

XPG is a causative gene underlying the photosensitive disorder xeroderma pigmentosum group G (XP-G) and is involved in nucleotide excision repair. Here, we show that XPG knockdown represses epidermal growth factor (EGF)-induced FOS transcription at the level of transcription elongation with little effect on EGF signal transduction. XPG interacted with transcription elongation factors in concert with TFIIH, suggesting that the XPG-TFIIH complex serves as a transcription elongation factor. The XPG-TFIIH complex was recruited to promoter and coding regions of both EGF-induced (FOS) and housekeeping (EEF1A1) genes. Further, EGF-induced recruitment of RNA polymerase II and TFIIH to FOS was reduced by XPG knockdown. Importantly, EGF-induced FOS transcription was markedly lower in XP-G/Cockayne syndrome (CS) cells expressing truncated XPG than in control cells expressing wild-type (WT) XPG, with less significant decreases in XP-G cells with XPG nuclease domain mutations. In corroboration of this finding, both WT XPG and a missense XPG mutant from an XP-G patient were recruited to FOS upon EGF stimulation, but an XPG mutant mimicking a C-terminal truncation from an XP-G/CS patient was not. These results suggest that the XPG-TFIIH complex is involved in transcription elongation and that defects in this association may partly account for Cockayne syndrome in XP-G/CS patients.
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PMID:Regulation of Transcription Elongation by the XPG-TFIIH Complex Is Implicated in Cockayne Syndrome. 2614 86


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