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)

Of three kinds of commercial zwitterionic detergents [SB 12, SB 14, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps)], SB 12 and Chaps were more useful than SB 14 because of high solubility and less interference with protein assay. Efficiency for protein solubilization at pH 6-9 was higher for SB 12 than for Chaps with either calf thymus chromatin or rat liver nuclei. At pH 9 and ionic strength (I) = 0.35, 1% SB 12 and 1% Chaps were capable of solubilizing about 70% and about 47% of total proteins in rat liver nuclei, respectively. Core histones in rat liver nuclei were extracted to a lesser extent with Chaps than with SB 12. DNA-dependent RNA polymerase and isopeptidase activities were barely inactivated by 1% Chaps at pH 8-9, but isopeptidase activity was inhibited by 0.3% SB 12. These facts indicate that whereas SB 12 is effective for solubilization of whole nuclear proteins, Chaps is suitable for the selective extraction of nonhistone chromosomal proteins without denaturation.
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PMID:Quantitative solubilization of nonhistone chromosomal proteins without denaturation using zwitterionic detergents. 409 Dec 62

Cajal bodies are nuclear structures that are involved in biogenesis of snRNPs and snoRNPs, maintenance of telomeres and processing of histone mRNA. Recently, the SUMO isopeptidase USPL1 was identified as a component of Cajal bodies that is essential for cellular growth and Cajal body integrity. However, a cellular function for USPL1 is so far unknown. Here, we use RNAi-mediated knockdown in human cells in combination with biochemical and fluorescence microscopy approaches to investigate the function of USPL1 and its link to Cajal bodies. We demonstrate that levels of snRNAs transcribed by RNA polymerase (RNAP) II are reduced upon knockdown of USPL1 and that downstream processes such as snRNP assembly and pre-mRNA splicing are compromised. Importantly, we find that USPL1 associates directly with U snRNA loci and that it interacts and colocalises with components of the Little Elongation Complex, which is involved in RNAPII-mediated snRNA transcription. Thus, our data indicate that USPL1 plays a key role in RNAPII-mediated snRNA transcription.
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PMID:A role for the Cajal-body-associated SUMO isopeptidase USPL1 in snRNA transcription mediated by RNA polymerase II. 2441 72

The ubiquitin-like SUMO system regulates gene expression, but the molecular insights into this process are incomplete. We show that the SUMO-specific isopeptidase SENP3 controls H3K4 methylation by regulating histone-modifying SET1/MLL complexes. SET1/MLL complexes are composed of a histone methyltransferase and the regulatory components WDR5, RbBP5, Ash2L, and DPY-30. MLL1/MLL2 complexes contain menin as additional component and are particularly important for the activation of HOX genes. We demonstrate that SENP3 is associated with MLL1/MLL2 complexes and catalyzes deSUMOylation of RbBP5. This is required for activation of a subset of HOX genes, including the developmental regulator DLX3. In the absence of SENP3, the association of menin and Ash2L with the DLX3 gene is impaired, leading to decreased H3K4 methylation and reduced recruitment of active RNA polymerase II. Importantly, the SENP3-DLX3 pathway dictates osteogenic differentiation of human stem cells, thus delineating the importance of balanced SUMOylation for epigenetic control of gene expression programs.
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PMID:The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation. 2493 Jul 34

Precise assembly of the sarcomere, a force-generating unit in striated muscles, is critical for muscle contraction. Defective sarcomere organization is linked to myopathies and cachexia. The molecular mechanisms concerning sarcomere assembly are poorly understood. Here, we report that the SUMO-specific isopeptidase SENP3 determines sarcomere assembly by specifically regulating the sarcomeric contractile myosin heavy-chain gene MyHC-II. The contractile ability of mature muscle cells is severely compromised in SENP3-depleted cells. Mechanistically, SENP3 is associated with the SETD7 histone methyltransferase and deSUMOylates SETD7. By recruiting SETD7 to MyHC-II, SENP3 promotes association of SETD7 with transcriptionally active RNA polymerase II and precludes the opposing methyltransferase Suv39h1. Strikingly, SENP3 is degraded in cachexia, characterized by dramatic loss of sarcomeric protein, particularly MyHC-II. SENP3 regulation of SETD7 is impaired in cachexia, leading to perturbed MyHC-II expression and disorganized sarcomeres. Our findings reveal an unanticipated role of SENP3 in sarcomere assembly and cachexia.
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PMID:Regulation of SETD7 Methyltransferase by SENP3 Is Crucial for Sarcomere Organization and Cachexia. 3114 94