Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic nucleotide PDEs (phosphodiesterases) regulate cellular levels of cAMP and cGMP by controlling the rate of degradation. Several mammalian PDE isoforms possess N-terminal GAF (found in cGMP PDEs, Anabaena adenylate cyclases and Escherichia coli FhlA; where FhlA is formate hydrogen lyase transcriptional activator) domains that bind cyclic nucleotides. Similarly, the CyaB1 and CyaB2 ACs (adenylate cyclases) of the cyanobacterium Anabaena PCC 7120 bind cAMP through one (CyaB1) or two (CyaB2) N-terminal GAF domains and mediate autoregulation of the AC domain. Sodium inhibits the activity of CyaB1, CyaB2 and mammalian PDE2A in vitro through modulation of GAF domain function. Furthermore, genetic ablation of cyaB1 and cyaB2 gives rise to Anabaena strains defective in homoeostasis at limiting sodium. Sodium regulation of GAF domain function has therefore been conserved since the eukaryotic/prokaryotic divergence. The GAF domain is the first identified protein domain to directly sense and signal changes in environmental sodium.
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PMID:Sodium regulation of GAF domain function. 1795 70

Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In this study, we investigated the transcriptional regulation of PDE3A , and found that the splicing factor proline and glutamine rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5'-rapid amplification of cDNA ends (RACE). Variable expression levels of three PDE3A variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of PDE3A -TSSs using chromatin immunoprecipitation sequencing (ChIP-seq). Serum-induced PDE3A expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of PDE3A In addition, transcription of PDE3A was lower in human cervical adenocarcinoma cells compared to normal cervical tissue. Furthermore, over-expression of PDE3A induced sensitivity to anti-cancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of PDE3A, which is involved in the regulation of DNMDP sensitivity , offering a novel molecular target for the development of anticancer therapies.
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PMID:SFPQ, a multifunctional nuclear protein, regulates the transcription of PDE3A. 2874 36