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

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

sigma B (sigma 37) is a secondary species of RNA polymerase sigma factor found in the gram-positive bacterium Bacillus subtilis. To study the function of sigma B genetically, we sought mutations that block the expression of a gene (ctc) known to be transcribed by sigma B-containing RNA polymerase in vitro. One such mutation, called crl, was found to map in or near the structural gene (sigB) for sigma B. To determine directly whether mutations in sigB would prevent transcription of ctc, we replaced sigB in the B. subtilis chromosome with insertion and deletion mutations that disrupted the sigma B coding sequence. Like crl, these in vitro-constructed mutations blocked expression of ctc, but had little or no effect on viability, sporulation, expression of the sporulation gene spoVG, or production of sporulation-associated alkaline protease. Using fusions of ctc to the reporter genes xylE and lacZ, we also identified mutations that enhanced ctc expression. One such mutation, called socB, was found to be located in an open reading frame immediately downstream of sigB.
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PMID:Genetic studies of a secondary RNA polymerase sigma factor in Bacillus subtilis. 311 22

Transcriptional stimulation by the model activator GAL4-VP16 (a chimeric protein consisting of the DNA-binding domain of the yeast activator GAL4 and the acidic activation domain of the herpes simplex virus protein VP16) involves a series of poorly understood protein-protein interactions between the VP16 activation domain and components of the RNA polymerase II general transcription machinery. One of these interactions is the VP16-mediated binding and recruitment of transcription factor TFIIB. However, TATA box-binding protein (TBP)-associated factors (TAFs), or coactivators, are required for this interaction to culminate in productive transcription complex assembly, and one such TAF, Drosophila TAF40, reportedly forms a ternary complex with VP16 and TFIIB. Due to TFIIB's central role in gene activation, we sought to directly visualize the surfaces of this protein that mediate formation of the ternary complex. We developed an approach called protease footprinting in which the broad-specificity proteases chymotrypsin and alkaline protease were used to probe binding of 32P-end-labeled TFIIB to GAL4-VP16 or TAF40. Analysis of the cleavage products revealed two regions of TFIIB protected by VP16 from protease attack, one of which overlapped with a region protected by TAF40. The close proximity of the VP16 and TAF40 binding sites on the surface of TFIIB suggests that this region could act as a regulatory interface mediating the effects of activators and coactivators on transcription complex assembly.
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PMID:Protease footprinting reveals a surface on transcription factor TFIIB that serves as an interface for activators and coactivators. 759 78

cDNA clone MS73 codes for an ATPase that is a regulatory subunit of the 26 S proteasome. Reverse transcriptase polymerase chain reaction analysis demonstrates that the expression of the gene dramatically increases in the pre-eclosion period. Western analyses show increases in other related. ATPases including MS73, MSS1, and mts2 but not TBP1. A similar increase in the 30-kDa subunit of the 20 S proteasome occurs. There are accompanying large changes in the peptidase activities of the 26 S proteasome. Relative to the 30-kDa subunit, there is no change in MSS1 and MS73, a 3-fold increase in mts2, and a 5-fold decline in TBP1. A large increase in the concentration of 26 S proteasomes together with extensive regulatory reprogramming may facilitate rapid muscular proteolysis.
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PMID:Developmental changes of the 26 S proteasome in abdominal intersegmental muscles of Manduca sexta during programmed cell death. 782 21

The SUG1 gene of Saccharomyces cerevisiae encodes a putative ATPase. Mutations in SUG1 were isolated as suppressors of a mutation in the transcriptional activation domain of GAL4. Sug1 was recently proposed to be a subunit of the RNA polymerase II holoenzyme and to mediate the association of transcriptional activators with holoenzyme. We show here that Sug1 is not a subunit of the holoenzyme, at least in its purified form, but of the 26S proteasome, a large complex of relative molecular-mass 2,000K that catalyses the ATP-dependent degradation of ubiquitin-protein conjugates. Sug1 co-purifies with the proteasome in both conventional and nickel-chelate affinity chromatography. Our observations account for the reduced ubiquitin-dependent proteolysis in sug1 mutants and suggest that the effects of sug1 mutations on transcription are indirect results of defective proteolysis.
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PMID:Identification of the gal4 suppressor Sug1 as a subunit of the yeast 26S proteasome. 862 1

Regulation of the membrane cofactor protein (MCP: CD46) was examined. While the expression of MCP in mice carrying MCP(BC2) cDNA with 125 bp of 3' untranslated region (3'UT) was minimal, that in mice carrying MCP cDNA without total 3' UT was evident in many organs. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis clearly showed the presence of mRNA even in transgenic mice with 3' UT, suggesting that the expression was regulated at the post-transcriptional stage. The in vitro expression data of MCP molecules on the stable Chinese hamster ovary (CHO) cell clone corresponded to that in transgenic mice. The first 125 bp downregulated the expression of MCP molecules in combination with not only beta-actin, but also SR alpha, promoter. Also, this region inhibited expression of decay accelerating factor (DAF: CD55) molecules when it was inserted into cDNA of DAF. Furthermore, the first 32 bp of the 3' UT revealed the same downregulation effect as 125 bp on MCP molecules. These findings indicated that the first 125 bp (and the first 32 bp in particular) of 3' UT regulate the expression of MCP molecules in transgenic mice.
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PMID:The regulation of membrane cofactor protein (CD46) expression by the 3' untranslated region in transgenic mice. 916 42

We have isolated a cDNA clone from mouse, m56, that encodes a member of the Conserved ATPase-containing Domain (CAD) protein family. Sequence analysis revealed that m56 is identical to mouse mSug1/FZA-B and shares high homology with human Trip1, moth 18-56, and yeast Sug1. When examined, Sug1-like CAD proteins appear to function in the regulation of the 26S proteasome, as well as associate with members of the steroid/thyroid receptor superfamily and other transcriptional activators. m56 can complement the lethal phenotype of loss of SUG1 in yeast. We have examined the tissue distribution of m56 using Northern and Western blots, in addition to immunocytochemistry and in situ hybridization. While m56 was expressed in all tissues and cells examined, several classes of neurons, most notably in the hippocampus, olfactory bulb, and cerebellum, displayed elevated levels of m56 mRNA and protein. We also examined distribution of RNA polymerase II and 26S proteasome subunit 4 (S4) within the mouse brain by in situ hybridization. While all three genes had similar patterns of expression, there were significant differences among them. In moths, the expression of the Sug1 homolog 18-56 is dramatically up-regulated during programmed cell death. In addition, it has been previously demonstrated that the proteasome plays an essential role in the regulation of apoptosis in mammals. We examined the expression of m56 in mouse during natural and induced cell death in a variety of tissues and found no significant changes in expression. Taken together, the data presented here suggest that while m56 is a highly conserved gene that presumably plays essential but complex roles in basal and developmental processes, it may not represent a rate-limiting step in these processes.
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PMID:Identification of a phylogenetically conserved Sug1 CAD family member that is differentially expressed in the mouse nervous system. 940 11

We have shown previously that UV radiation and other DNA-damaging agents induce the ubiquitination of a portion of the RNA polymerase II large subunit (Pol II LS). In the present study UV irradiation of repair-competent fibroblasts induced a transient reduction of the Pol II LS level; new protein synthesis restored Pol II LS to the base-line level within 16-24 h. In repair-deficient xeroderma pigmentosum cells, UV radiation-induced ubiquitination of Pol II LS was followed by a sustained reduction of Pol II LS level. In both normal and xeroderma pigmentosum cells, the ubiquitinated Pol II LS had a hyperphosphorylated COOH-terminal domain (CTD), which is characteristic of elongating Pol II. The portion of Pol II LS whose steady-state level diminished most quickly had a relatively hypophosphorylated CTD. The ubiquitinated residues did not map to the CTD. Importantly, UV-induced reduction of Pol II LS level in repair-competent or -deficient cells was inhibited by the proteasome inhibitors lactacystin or MG132. These data demonstrate that UV-induced ubiquitination of Pol II LS is followed by its degradation in the proteasome. These results suggest, contrary to a current model of transcription-coupled DNA repair, that elongating Pol II complexes which arrest at intragenic DNA lesions may be aborted rather than resuming elongation after repair takes place.
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PMID:Ultraviolet radiation-induced ubiquitination and proteasomal degradation of the large subunit of RNA polymerase II. Implications for transcription-coupled DNA repair. 947 72

The mechanisms by which the p53 response is triggered following exposure to DNA-damaging agents have not yet been clearly elucidated. We and others have previously suggested that blockage of RNA polymerase II may be the trigger for induction of the p53 response following exposure to ultraviolet light. Here we report on the correlation between inhibition of mRNA synthesis and the induction of p53, p21WAF1 and apoptosis in diploid human fibroblasts treated with either UV light, cisplatin or the RNA synthesis inhibitors actinomycin D, DRB, H7 and alpha-amanitin. Exposure to ionizing radiation or the proteasome inhibitor LLnL, however, induced p53 and p21WAF1 without affecting mRNA synthesis. Importantly, induction of p53 by the RNA synthesis or proteasome inhibitors did not correlate with the induction of DNA strand breaks. Furthermore, cisplatin-induced accumulation of active p53 in repair-deficient XP-A cells occurred despite the lack of DNA strand break induction. Our results suggest that the induction of the p53 response by certain toxic agents is not triggered by DNA strand breaks but rather, may be linked to inhibition of mRNA synthesis either directly by the poisoning of RNA polymerase II or indirectly by the induction of elongation-blocking DNA lesions.
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PMID:Inhibition of RNA polymerase II as a trigger for the p53 response. 998 8

The yeast CTDK-I complex has been implicated in phosphorylation of the carboxy-terminal domain of the RNA polymerase II and in transcription control. It is composed of three polypeptides: Ctk1p and Ctk2p, a cyclin-dependent kinase and a C-type cyclin subunit, respectively; and Ctk3p, a third subunit of unknown function. Cyclins are regulatory proteins whose expression is tightly controlled at the protein level. In this study, we examined the regulation of Ctk2p expression in vivo. Surprisingly, unlike what has been described for cell cycle cyclins, steady-state levels of Ctk2p are composed of two relatively abundant forms, one of them phosphorylated. We show that this phosphorylated form is extremely unstable (half-life, 5 min) and that rapid proteolysis of Ctk2p exhibits growth-related regulation. Furthermore, our data establish that similar to the case for other naturally short-lived proteins, Ctk2p degradation is mediated by the ubiquitin-proteasome pathway. This is the first demonstration that a C-type cyclin is phosphorylated and targeted to the proteasome. Strikingly, neither phosphorylation nor destruction of Ctk2p requires its associated kinase Ctk1p, a feature fundamentally different from that which has been observed for cell cycle cyclins.
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PMID:The yeast C-type cyclin Ctk2p is phosphorylated and rapidly degraded by the ubiquitin-proteasome pathway. 1008 18

Rsp5 is an E3 ubiquitin-protein ligase of Saccharomyces cerevisiae that belongs to the hect domain family of E3 proteins. We have previously shown that Rsp5 binds and ubiquitinates the largest subunit of RNA polymerase II, Rpb1, in vitro. We show here that Rpb1 ubiquitination and degradation are induced in vivo by UV irradiation and by the UV-mimetic compound 4-nitroquinoline-1-oxide (4-NQO) and that a functional RSP5 gene product is required for this effect. The 26S proteasome is also required; a mutation of SEN3/RPN2 (sen3-1), which encodes an essential regulatory subunit of the 26S proteasome, partially blocks 4-NQO-induced degradation of Rpb1. These results suggest that Rsp5-mediated ubiquitination and degradation of Rpb1 are components of the response to DNA damage. A human WW domain-containing hect (WW-hect) E3 protein closely related to Rsp5, Rpf1/hNedd4, also binds and ubiquitinates both yeast and human Rpb1 in vitro, suggesting that Rpf1 and/or another WW-hect E3 protein mediates UV-induced degradation of the large subunit of polymerase II in human cells.
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PMID:Rsp5 ubiquitin-protein ligase mediates DNA damage-induced degradation of the large subunit of RNA polymerase II in Saccharomyces cerevisiae. 1049 Jun 34


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