The PP2A-A beta Gene is Regulated by Multiple Transcriptional Factors Including Ets-1, SP1/SP3, and RXR alpha/beta

文献类型： 外文期刊

第一作者： Liu, J.

作者： Liu, J.;Chen, P. -C.;Hu, W. -F.;Hu, X.;Liu, W. -B.;Xiao, Y. -M.;Liang, S. -P.;Liu, Y.;Liu, S. -J.;Li, D. W. -C.;Liu, J.;Ji, W.;Sun, S.;Zhang, L.;Chen, H. -G.;Zhang, X.;Gong, L.;Deng, M.;Chen, P. -C.;Hu, W. -F.;Hu, X.;Liu, J.;Woodward, Z.;Li, D. W. -C.;Li, D. W. -C.;Liu, J.;Sun, S.;Zhang, L.;Chen, H. -G.;Mao, Y.;Liu, L.;Gong, L.;Deng, M.;Deng, M.;Chen, L.;Han, W. -J.

作者机构：

关键词： Protein phosphorylation;dephosphorylation;PP-2A;PP2A-A beta;gene regulation;Ets;SP1;SP3;RXR alpha/beta;lens;retina;cataract;cancer

期刊名称：CURRENT MOLECULAR MEDICINE （ 影响因子：2.222； 五年影响因子：3.084 ）

ISSN： 1566-5240

年卷期： 2012 年 12 卷 8 期

页码：

收录情况： SCI

摘要： Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65kD scaffold A subunit, a 36kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130kDs. The scaffold subunits, PP2A-A alpha/beta, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-A alpha and PP2A-A beta lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-A alpha is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2 alpha but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-A beta gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXR alpha/beta, are present in the proximal promoter of the mouse PP2A-A beta gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXR alpha/beta all bind to PP2A-A beta gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXR alpha/beta positively regulate the promoter of the PP2A-A beta gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXR alpha/beta and the luciferase reporter gene driven by PP2A-A promoter further confirm their control over the PP2A-A beta promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXR alpha/beta can all bind to the PP2A-A beta gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-A beta gene. Moreover, our results provide important information explaining why PP2A-A alpha and PP2A-A beta display distinct expression levels.

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