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)

NF-E2 is an erythroid-specific transcription factor required for expression of several erythroid-specific genes. By Far-Western blotting and yeast two-hybrid assay, we demonstrate that p45, the large subunit of NF-E2, is capable of binding to a specific set of WW domain-containing proteins, including the ubiquitin ligase hRPF1. This binding is mediated through the interaction between the WW domains and a PY motif located within the amino-terminal region of p45. Interestingly, the carboxyl-terminal domain of mammalian RNA polymerase II binds a similar set of WW domains to which p45 interacts with. We discuss the data in terms of possible new pathways through which the processes of transcriptional regulation by NF-E2 could be regulated in erythroid and megakaryote cells.
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PMID:Interaction of WW domains with hematopoietic transcription factor p45/NF-E2 and RNA polymerase II. 930 52

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

We showed previously that the WW domain of the prolyl isomerase, Ess1, can bind the phosphorylated carboxyl-terminal domain (phospho-CTD) of the largest subunit of RNA Polymerase II. Analysis of phospho-CTD binding by four other WW domain-containing Saccharomyces cerevisiae proteins indicates the splicing factor, Prp40, and the RNA polymerase II ubiquitin ligase, Rsp5, can also bind the phospho-CTD. The identification of Prp40 as a phospho-CTD binding protein represents the first demonstration of direct interaction between a documented splicing factor and the phospho-CTD. Domain dissection studies reveal that phospho-CTD binding occurs at multiple locations in Prp40, including sites in both the WW and FF domain regions. Because the conserved repeats of the CTD make it an ideal ligand for multi-site binding events, the implications of multi-site binding are discussed. Our data suggest a mechanism by which the phospho-CTD of elongating RNA polymerase II facilitates commitment complex formation by juxtaposing the 5' and 3' splice sites.
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PMID:The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II. 1097 20

The WW domain is a protein module found in a wide range of signaling proteins. It is one of the smallest protein modules that folds as a monomer without disulfide bridges or cofactors. WW domains bind proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. Although the WW domain was initially considered a 'cytoplasmic module', the proteins containing WW domains have also been localized in the cell nucleus. Moreover, these proteins have been documented to participate in co-activation of transcription and modulation of RNA polymerase II activity. The carboxy-terminal domain (CTD) of RNA polymerase II acts as an assembly platform for distinct WW domain-containing proteins that affect the function of the RNA polymerase II. The formation of complexes between CTD and WW domain-containing proteins is regulated by phosphorylation of the CTD. Since the CTD sequence is highly repetitive and a target of several post-translational modifications and conformational changes, it presents a unique structure capable of enormous molecular diversity. The WW domain has been implicated in several human diseases including Alzheimer's disease. The WW domain-containing iso-prolyl isomerase named Pin1, a protein known to be essential for cell cycle progression, was shown to be active in restoration of the microtubule-binding activity of Tau, a protein of neurofibrillar tangles found in the brains of Alzheimer's patients. It is the WW domain of Pin1 that interacts directly with Tau protein. In addition, the WW domain-containing adapter protein FE65 was shown to regulate processing of Alzheimer's amyloid precursor protein. It is expected that by understanding the details of the WW domain-mediated protein-protein interactions, we will be able to illuminate numerous signaling pathways which control certain aspects of transcription and cell cycle.
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PMID:Functions of WW domains in the nucleus. 1122 34

Phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II) largest subunit has an important role in transcription elongation and in coupling transcription to pre-mRNA processing. To identify proteins that can directly bind to the phosphorylated CTD, we screened a human cDNA expression library using 32P-labeled CTD as a probe. Here we report the cloning and characterization of a novel human WW domain-containing protein, PCIF1 (phosphorylated CTD interacting factor 1). PCIF1 is composed of 704 amino acids. The WW domain of PCIF1 can directly and preferentially bind to the phosphorylated CTD compared to the unphosphorylated CTD. PCIF1 binds to the hyperphosphorylated RNAP II (RNAP IIO) in vitro and in vivo. Double immunofluorescence labeling in HeLa cells demonstrated that PCIF1 and endogenous RNAP IIO are co-localized in the cell nucleus. Thus, PCIF1 may play a role in mRNA synthesis by modulating RNAP IIO activity.
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PMID:PCIF1, a novel human WW domain-containing protein, interacts with the phosphorylated RNA polymerase II. 1256 71

The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) largest subunit undergoes reversible phosphorylation during transcription cycle. The phosphorylated CTD plays critical roles in coordinating transcription with chromatin modification and RNA processing by serving as a scaffold to recruit various proteins. Recently, we identified a novel human WW domain-containing protein PCIF1 as a phosphorylated CTD-interacting factor and demonstrated that PCIF1 negatively modulates Pol II activity in vivo. In the present study, to explore cellular functions of PCIF1, we generated PCIF1-deficient chicken DT40 cell lines. We observed significant up-regulation of WW domain-containing prolyl isomerase Pin1 in two independently established PCIF1-deficient mutant clones. As reconstitution of PCIF1 in the mutants did not reduce Pin1 expression, PCIF1 may not be a negative regulator of Pin1 expression. We assume that Pin1 over-expression might suppress defects caused by PCIF1 deficiency in DT40 cells. We furthermore compared PCIF1 and Pin1 for their functional properties and found that these two proteins exhibit most similar target specificity among other CTD-binding WW proteins, overlapping subcellular localization and comparative inhibitory effects on transcriptional activation by Pol II in human cultured cells. These results suggest that Pin1 may have overlapping cellular function with PCIF1 in vertebrate cells.
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PMID:Prolyl isomerase Pin1 shares functional similarity with phosphorylated CTD interacting factor PCIF1 in vertebrate cells. 1968 92