Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genes transcribed by RNA polymerase II are silenced when introduced near the mat2 or mat3 mating-type loci of the fission yeast Schizosaccharomyces pombe. Silencing is mediated by a number of gene products and cis-acting elements. We report here the finding of novel trans-acting factors identified in a screen for high-copy-number disruptors of silencing. Expression of cDNAs encoding the putative E2 ubiquitin-conjugating enzymes UbcP3, Ubc15 (ubiquitin-conjugating enzyme), or Rhp6 (Rad homolog pombe) from the strong nmt1 promoter derepressed the silent mating-type loci mat2 and mat3 and reporter genes inserted nearby. Deletion of rhp6 slightly derepressed an ade6 reporter gene placed in the mating-type region, whereas disruption of ubcP3 or ubc15 had no obvious effect on silencing. Rhp18 is the S. pombe homolog of Saccharomyces cerevisiae Rad18p, a DNA-binding protein that physically interacts with Rad6p. Rhp18 was not required for the derepression observed when UbcP3, Ubc15, or Rhp6 was overproduced. Overexpressing Rhp6 active-site mutants showed that the ubiquitin-conjugating activity of Rhp6 is essential for disruption of silencing. However, high dosage of UbcP3, Ubc15, or Rhp6 was not suppressed by a mutation in the 26S proteasome, suggesting that loss of silencing is not due to an increased degradation of silencing factors but rather to the posttranslational modification of proteins by ubiquitination. We discuss the implications of these results for the possible modes of action of UbcP3, Ubc15, and Rhp6.
...
PMID:The fission yeast ubiquitin-conjugating enzymes UbcP3, Ubc15, and Rhp6 affect transcriptional silencing of the mating-type region. 1245 9

When mammalian cells are exposed to cisplatin or ultraviolet irradiation, the RNA polymerase II (RNAP II) large subunit becomes ubiquitinated and is subsequently degraded via the proteasomal pathway. Using a DNA template immobilized on magnetic beads in an in vitro transcription reaction, we showed that a pause of the elongating RNAP II complex caused by nucleotide starvation induced the ubiquitination of the stalled RNAP II. The ubiquitinated RNAP II dissociated from the ternary complex when transcription was allowed to resume. The dissociated (free) RNAP II remained ubiquitinated. The proteasome inhibitor MG132 increased the accumulation of ubiquitinated free RNAP II but did not affect the amount of ubiquitinated, template-bound RNAP II, indicating that the ubiquitinated RNAP II was displaced from the template and then degraded by the proteasomes. Our work shows that the elongation complex that was stalled at the template by nucleotide starvation is targeted by the ubiquitin-conjugating system and that ubiquitination facilitates displacement of the stalled RNAP II from the template. Our findings together with the findings by others that DNA damaging agents induced the ubiquitination in mammalian cells that are nucleotide excision repair competent, suggest that the RNAP II ubiquitination may have a role in the regulation of transcription-coupled DNA repair.
...
PMID:RNA polymerase II stalled on a DNA template during transcription elongation is ubiquitinated and the ubiquitination facilitates displacement of the elongation complex. 1257 24

The hepatitis A virus 3C protease and 3D RNA polymerase are present in low concentrations in infected cells. The 3C protease was previously shown to be rapidly degraded by the ubiquitin/26S proteasome system and we present evidence here that the 3D polymerase is also subject to ubiquitination-mediated proteolysis. Our results show that the sequence (32)LGVKDDWLLV(41) in the 3C protease serves as a protein destruction signal recognized by the ubiquitin-protein ligase E3alpha and that the destruction signal for the RNA polymerase does not require the carboxyl-terminal 137 amino acids. Both the viral 3ABCD polyprotein and the 3CD diprotein were also found to be substrates for ubiquitin-mediated proteolysis. Attempts to determine if the 3C protease or the 3D polymerase destruction signals trigger the ubiquitination and degradation of these precursors yielded evidence suggesting, but not unequivocally proving, that the recognition of the 3D polymerase by the ubiquitin system is responsible.
...
PMID:Signals in hepatitis A virus P3 region proteins recognized by the ubiquitin-mediated proteolytic system. 1275 77

The toxin target (TOT) function of the Saccharomyces cerevisiae Elongator complex enables Kluyveromyces lactis zymocin to induce a G1 cell cycle arrest. Loss of a ubiquitin-related system (URM1-UBA4 ) and KTI11 enhances post-translational modification/proteolysis of Elongator subunit Tot1p (Elp1p) and abrogates its TOT function. Using TAP tagging, Kti11p contacts Elongator and translational proteins (Rps7Ap, Rps19Ap Eft2p, Yil103wp, Dph2p). Loss of YIL103w and DPH2 (involved in diphtheria toxicity) suppresses zymocicity implying that both toxins overlap in a manner mediated by Kti11p. Among the pool that co-fractionates with RNA polymerase II (pol II) and nucleolin, Nop1p, unmodified Tot1p dominates. Thus, modification/proteolysis may affect association of Elongator with pol II or its localization. Consistently, an Elongator-nuclear localization sequence (NLS) targets green fluorescent protein (GFP) to the nucleus, and its truncation yields TOT deficiency. Similarly, KAP120 deletion rescues cells from zymocin, suggesting that Elongator's TOT function requires NLS- and karyopherin-dependent nuclear import.
...
PMID:Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification. 1294 Sep 88

Phylogenetic analysis of small and large subunits of rDNA genes suggested that Foraminifera originated early in the evolution of eukaryotes, preceding the origin of other rhizopodial protists. This view was recently challenged by the analysis of actin and ubiquitin protein sequences, which revealed a close relationship between Foraminifera and Cercozoa, an assemblage of various filose amoebae and amoeboflagellates that branch in the so-called crown of the SSU rDNA tree of eukaryotes. To further test this hypothesis, we sequenced a fragment of the largest subunit of the RNA polymerase II (RPB1) from five foraminiferans, two cercozoans and the testate filosean Gromia oviformis. Analysis of our data confirms a close relationship between Foraminifera and Cercozoa and points to Gromia as the closest relative of Foraminifera.
...
PMID:Foraminifera and Cercozoa share a common origin according to RNA polymerase II phylogenies. 1465 1

Apoptosis-antagonizing transcription factor (AATF), also termed Che-1, was identified as interacting protein of Dlk/ZIP kinase and RNA polymerase II, respectively. Che-1 has additionally been shown to bind Rb, thereby activating transcription factor E2F and promoting cell cycle progression. Moreover, AATF enhances steroid receptor-mediated transactivation in a hormone- and dose-dependent manner (Leister, P., Burgdorf, S., and Scheidtmann, K. H., (2003) Signal Transduction 3, 18-25). These data suggest that AATF exerts its functions through interaction with different transcription factors. In search of novel interaction partners of AATF, we identified the tumor susceptibility gene product TSG101, which had also been recognized as a co-regulator of nuclear hormone receptors. Interestingly, TSG101 and AATF functioned as cooperative coactivators in androgen receptor-mediated transcription. Because TSG101 was also shown to play a role in regulation of ubiquitin conjugation, we asked whether its coactivating function might be linked to ubiquitination. Indeed, TSG101 enhanced monoubiquitination of the androgen receptor in a ligand-dependent manner, and this correlated with enhanced transactivating capacity. Furthermore, a dominant-negative mutant of ubiquitin preventing polyubiquitination also stimulated androgen receptor-mediated transcription, which in this case could not be enhanced by TSG101. We propose that TSG101 activates androgen receptor-induced transcription by transient stabilization of the monoubiquitinated state, thus revealing a novel regulatory mechanism for nuclear receptors.
...
PMID:TSG101 interacts with apoptosis-antagonizing transcription factor and enhances androgen receptor-mediated transcription by promoting its monoubiquitination. 1476 44

Recent studies from a number of laboratories have revealed a surprising number of connections between RNA polymerase II transcription and the ubiquitin/proteasome pathway. We now find yet another intersection of these pathways by showing that the 26S proteasome associates with regions of the GAL1, GAL10, and HSP82 genes, including the 3' ends, in a transcription-dependent fashion. The appearance of the proteasome on these inducible genes correlates with both the accumulation of transcripts and the buildup of RNA polymerase II complexes in the same region. Furthermore, the 26S proteasome and RNA polymerase II coimmunoprecipitate, and inhibition of 26S proteolytic activity leads to increased read through of a transcription termination site. We suggest that the proteasome is generally recruited to the DNA at sites of stalled RNA polymerase and may act to resolve these complexes.
...
PMID:Physical and functional association of RNA polymerase II and the proteasome. 1506 96

Acidic or type IIB transcriptional activation domains (AADs) increase rates of initiation as well as elongation of transcription. For the former effects, AADs bind general transcription factors and larger coactivator complexes, which position RNA polymerase II (RNAPII) at sites of initiation of transcription. For the latter effects, their ubiquitylation plays an important role. In this study, this posttranslational modification increased the binding between a prototypic AAD and the positive transcription elongation factor b (P-TEFb), which contains a C-type cyclin (CycT1, CycT2, or CycK) and Cdk9. By phosphorylating negative elongation factors and the C-terminal domain of RNAPII, P-TEFb modifies the transcription complex for efficient elongation and cotranscriptional processing of mRNA. Indeed, the activation domain of VP16 and ubiquitin bound the cyclin boxes and the C terminus in CycT1, respectively. Moreover, the artificial fusion of ubiquitin with VP16 not only increased its activity via DNA and RNA, which was reflected in increased ratios of elongated to initiated transcripts, but rescued the deleterious substitution of alanine for phenylalanine at position 442 in its AAD. Thus, the ubiquitylation of AADs increases their interaction with P-TEFb and augments rates of elongation of transcription.
...
PMID:VP16 and ubiquitin; binding of P-TEFb via its activation domain and ubiquitin facilitates elongation of transcription of target genes. 1529 79

Agonist-mediated degradation of estrogen receptor alpha (ERalpha) has been associated with its transcriptional activity. However, the mechanism by which ERalpha is targeted for degradation and whether there is a direct functional link between ERalpha stability and ERalpha-mediated transactivation have not been elucidated. Here we provide evidence that the p160 coactivator, AIB1, uniquely mediates agonist-induced, but not antagonist-induced, ERalpha degradation. We show that AIB1 recruitment by ERalpha is not only necessary but also sufficient to promote degradation. Suppression of AIB1 levels leads to ERalpha stabilization in the presence of 17beta-estradiol and, despite increased ERalpha levels, reduced recruitment of ERalpha to endogenous target gene promoters. In addition, association of RNA polymerase II with ERalpha target promoters is lost when AIB1 is suppressed, leading to inhibition of target gene transcription. AIB1 thus plays a dual role in regulating ERalpha activity, one in recruiting transcription factors including other coactivators involved in gene activation and the other in regulating ERalpha protein degradation mediated by the ubiquitin-proteosome machinery.
...
PMID:Coactivator AIB1 links estrogen receptor transcriptional activity and stability. 1528 19

The TFIID complex is composed of the TATA-binding protein (TBP) and TBP-associated factors (TAFs) and is the only component of the general RNA polymerase II (RNAP II) transcription machinery with intrinsic sequence-specific DNA-binding activity. Binding of transcription factor (TF) IID to the core promoter region of protein-coding genes is a key event in RNAP II transcription activation and is the first and rate-limiting step of transcription initiation complex assembly. Intense research efforts in the past have established that TFIID promoter-binding activity as well as the function of TFIID-promoter complexes is tightly regulated through dynamic TFIID interactions with positive- and negative-acting transcription regulatory proteins. However, very little is known about the role of post-translational modifications in the regulation of TFIID. Here we show that the human TFIID subunits hsTAF5 and hsTAF12 are modified by the small ubiquitin-related modifier SUMO-1 in vitro and in human cells. We identify Lys-14 in hsTAF5 and Lys-19 in hsTAF12 as the primary SUMO-1 acceptor sites and show that SUMO conjugation has no detectable effect on nuclear import or intranuclear distribution of hsTAF5 and hsTAF12. Finally, we demonstrate that purified human TFIID complex can be SUMO-1-modified in vitro at both hsTAF5 and hsTAF12. We find that SUMO-1 conjugation at hsTAF5 interferes with binding of TFIID to promoter DNA, whereas modification of hsTAF12 has no detectable effect on TFIID promoter-binding activity. Our observations suggest that reversible SUMO modification at hsTAF5 contributes to the dynamic regulation of TFIID promoter-binding activity in human cells.
...
PMID:SUMO-1 modification of human transcription factor (TF) IID complex subunits: inhibition of TFIID promoter-binding activity through SUMO-1 modification of hsTAF5. 1563 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---