Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the PITSLRE protein kinases are members of the cyclin-dependent kinase superfamily, their cellular function is unclear. Previously we demonstrated that the general RNA splicing factor RNPS1 is a specific PITSLRE p110 kinase interactor in vivo. This suggests that the PITSLRE family of protein kinases is involved in some aspect of RNA processing or transcription. Here we identify multiple transcriptional elongation factors, including ELL2, TFIIF(1), TFIIS, and FACT, as PITSLRE kinase-associated proteins. We demonstrate that PITSLRE p110 protein kinases co-immunoprecipitate and/or co-purify with these elongation factors as well as with RNA polymerase II. Antibody-mediated inhibition of PITSLRE kinase specifically suppressed RNA polymerase II-dependent in vitro transcription initiated at a GC-rich (adenosine deaminase) or TATA box-dependent (Ad2ML) promoter, and this suppression was rescued by readdition of purified PITSLRE p110 kinase. Together, these data strongly suggest that PITSLRE protein kinases participate in a signaling pathway that potentially regulates or links transcription and RNA processing events.
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PMID:PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. 1170 59

Adenosine-to-inosine RNA editing has been recently implicated in the pathogenesis of inflammation through the upregulation of the editase adenosine deaminase acting on RNA 1 (ADAR1). Because cell proliferation is a key feature of the inflammatory process, the present study tested the hypothesis that overexpression of ADAR1 accelerates cell cycle. To that end, human embryonic kidney 293 cells were transiently transfected with ADAR1 or vector, and cell cycle was evaluated by fluorescence-activated cell sorter. Overexpression of wild-type ADAR1 decreased the proportion of G0-G1 cells (-19%, P<0.01, n=3), increased the percentage of S phase cells (+19%, P<0.01, n=3), and did not change the ratio of cells residing in the G2-M phase (n=3). This finding was supported by three observations. First, there was a parallel production in ADAR1-transfected cells of cyclin-dependent kinase (Cdk) 2 and cyclin A, a pivotal protein complex upregulated at the G1-S phase checkpoint, and of [p]-Histone H1, a marker of Cdk2 activity (+102%, P<0.01, n=3). Second, ADAR1-transfected cells displayed higher activity of the proliferation marker, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide. Third, using anti-ADAR1 antibody, direct binding of ADAR1 to Cdk2 messenger RNA was demonstrated in ADAR1-transfected cells by protein-RNA cross-linking and immunoprecipitation (+974%, P<0.01, n=3). Finally, causal relationships between ADAR1 and Cdk2 were confirmed by a study with the Cdk2 inhibitor, kenpaullone, which prevented the ADAR1-induced shift from the G0-G1 to the S phase. Taken together, these data show that ADAR1 increases cell cycle by shifting cells from the G0-G1 to the S phase through the upregulation of Cdk2.
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PMID:Adenosine deaminase acting on RNA 1 accelerates cell cycle through increased translation and activity of cyclin-dependent kinase 2. 1722 99