Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enhancer-binding protein NIFA is required for transcriptional activation of nif promoters by the alternative holoenzyme form of RNA polymerase, which contains the sigma factor sigma 54 (sigma N). NIFA hydrolyzes nucleoside triphosphates to catalyze the isomerization of closed promoter complexes to transcriptionally competent open complexes. The activity of NIFA is antagonized by the regulatory protein NIFL in response to oxygen and fixed nitrogen in vivo. We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter. Open complexes formed by sigma 54-containing RNA polymerase are considerably more stable to heparin challenge in the presence of GTP than in the presence of ATP. This differential stability is most probably a consequence of GTP being the initiating nucleotide at this promoter. Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions. We propose a model in which NIFL modulates the activity of NIFA via an adenosine nucleotide switch.
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PMID:Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL. 786 90

The NIFA protein of Klebsiella pneumoniae is required for transcription of all nif (nitrogen fixation) operons except the regulatory nifLA operon itself. NIFA activates transcription of nif operons by the alternative holoenzyme form of RNA polymerase, sigma 54-holoenzyme, in a nucleoside triphosphate (NTP)-dependent manner. NIFL antagonizes the action of NIFA in the presence of molecular oxygen or combined nitrogen. The NIFA protein of K. pneumoniae is composed of three domains: an N-terminal domain with unclear function, a central catalytic domain, and a C-terminal DNA-binding domain. We report that the isolated central domain of NIFA activates transcription in vitro and that this activation requires NTP with a hydrolyzable beta-gamma bond, as does activation by intact NIFA. Transcriptional activation by the isolated central domain has the heat lability characteristic of intact NIFA and is inhibited by NIFL. The central domain has an NTPase activity that is also heat-labile but is not inhibited by NIFL. Taken together, these results imply that NIFL interferes with contact between NIFA and sigma 54-holoenzyme.
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PMID:The isolated catalytic domain of NIFA, a bacterial enhancer-binding protein, activates transcription in vitro: activation is inhibited by NIFL. 827 50

The Azotobacter vinelandii NIFL regulatory flavoprotein responds to the redox, energy and nitrogen status of the cell to inhibit transcriptional activation by the sigmaN-dependent enhancer binding protein, NIFA, via the formation of a NIFL-NIFA protein complex. The NIFA protein contains three domains: an N-terminal domain of unknown function; a central catalytic domain required to couple nucleotide hydrolysis to activation of the sigmaN-RNA polymerase holoenzyme; and a C-terminal DNA-binding domain. We report that truncated NIFA proteins that either lack the amino-terminal domain or contain only the isolated central domain remain responsive to inhibition by NIFL but, in contrast to native NIFA, continue to hydrolyse nucleotides when NIFL is present. We also report that NIFL is competent to inhibit the DNA-binding function of NIFA. Taken together, these results suggest that NIFL inhibits NIFA via a concerted mechanism in which DNA binding, catalytic activity and, potentially, interaction with the polymerase are controlled by NIFL in order to prevent transcriptional activation under detrimental environmental conditions.
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PMID:Concerted inhibition of the transcriptional activation functions of the enhancer-binding protein NIFA by the anti-activator NIFL. 1113 67

Chromosome 3p21.3 region is frequently (>90%) deleted in lung and other major human carcinomas. We subdivided 3p21.3 into LUCA and AP20 subregions and discovered frequent homozygous deletions (10-18%) in both subregions. This finding strongly implies that they harbor multiple tumor suppressor genes involved in the origin and/or development of major epithelial cancers. In this study, we performed an initial analysis of RBSP3/HYA22, a candidate tumor suppressor genes located in the AP20 region. Two sequence splice variants of RBSP3/HYA22 (A and B) were identified, and we provide evidence for their tumor suppressor function. By sequence analysis RBSP3/HYA22 belongs to a gene family of small C-terminal domain phosphatases that may control the RNA polymerase II transcription machinery. Expression of the gene was drastically (>20-fold) decreased in 11 of 12 analyzed carcinoma cell lines and in three of eight tumor biopsies. We report missense and nonsense mutations in tumors where RBSP3/HYA22 was expressed, growth suppression with regulated transgenes in culture, suppression of tumor formation in severe combined immunodeficient mice, and dephosphorylation of ppRB by RBSP3/HYA22, presumably leading to a block of the cell cycle at the G1/S boundary.
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PMID:RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies. 1505 89

The functional association between intronic miRNAs and their host genes is still largely unknown. We found that three gene loci, which produced miR-26a and miR-26b, were embedded within introns of genes coding for the proteins of carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase (CTDSP) family, including CTDSPL, CTDSP2 and CTDSP1. We conducted serum starvation-stimulation assays in primary fibroblasts and two-thirds partial-hepatectomies in mice, which revealed that miR-26a/b and CTDSP1/2/L were expressed concomitantly during the cell cycle process. Specifically, they were increased in quiescent cells and decreased during cell proliferation. Furthermore, both miR-26 and CTDSP family members were frequently downregulated in hepatocellular carcinoma (HCC) tissues. Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression. Further investigation disclosed that miR-26a/b directly suppressed the expression of CDK6 and cyclin E1, which resulted in reduced phosphorylation of pRb. Moreover, c-Myc, which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition. Our findings highlight the functional association of miR-26a/b and their host genes and provide new insight into the regulatory network of the G1/S-phase transition.
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PMID:MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein. 2221 Aug 97