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      저자 : Hockman, Steven  (검색결과 1 건)
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      • SFPQ, a multifunctional nuclear protein, regulates the transcription of <i>PDE3A</i>

        Rhee, Dong ,Keun,Hockman, Steven ,C.,Choi, Sunkyung,Kim, Yong-Eun,Park, Chungoo,Manganiello, Vincent ,C.,Kim, Kee ,K. Portland Press Ltd. 2017 Bioscience reports Vol.37 No.4

        <P>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 <I>PDE3A</I> gene expression remain largely unknown. In the present study, we investigated the transcriptional regulation of <I>PDE3A</I>, and found that the splicing factor proline- and glutamine-rich (SFPQ) protein modulated <I>PDE3A</I> mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of <I>PDE3A</I> using 5′-rapid amplification of cDNA ends (RACE). Variable expression levels of three <I>PDE3A</I> variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of <I>PDE3A</I>-TSSs using ChIP sequencing (ChIP-seq). Serum-induced <I>PDE3A</I> expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of <I>PDE3A</I>. In addition, transcription of <I>PDE3A</I> was lower in human cervical adenocarcinoma cells compared with normal cervical tissue. Furthermore, overexpression of <I>PDE3A</I> induced sensitivity to anticancer 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 <I>PDE3A</I>, which is involved in the regulation of DNMDP sensitivity, offering a novel molecular target for the development of anticancer therapies.</P>

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