Transcriptional regulation of PP2A-A alpha is mediated by multiple factors including AP-2alpha, CREB, ETS-1, and SP-1.
Transcriptional regulation of PP2A-A alpha is mediated by multiple factors including AP-2alpha, CREB, ETS-1, and SP-1.
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DOI：
10.1371/journal.pone.0007019
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发表时间：
2009-09-14
期刊：
影响因子：
3.7
通讯作者：
Li DW
中科院分区：
文献类型：
--
作者：
Chen HG;Han WJ;Deng M;Qin J;Yuan D;Liu JP;Xiao L;Gong L;Liang S;Zhang J;Liu Y;Li DW
蛋白磷酸酶-2A(PP-2A)是一种主要的丝氨酸/苏氨酸磷酸酶，在真核生物中占50%以上的丝氨酸/苏氨酸磷酸酶活性。PP-2A的全酶由骨架A亚基、催化C亚基和调节B亚基组成。支架亚基PP2A-Aα/β为C亚基和B亚基提供了结合的平台，从而在提供特定的PP-2A活性方面发挥了关键作用。编码PP2A-Aα/β的两个基因的突变会导致癌症发生，并可能导致其他人类疾病。细胞外和细胞内的各种因素对这些基因的调控在很大程度上仍不清楚。在本研究中，我们对小鼠PP2A-Aα基因的启动子进行了功能剖析。我们的结果表明，小鼠PP2A-Aα基因启动子的近端除了含有TFIIB结合位点(BRE)和下游启动子元件(Dpe)外，还含有许多与CREB、Ets-1、AP-2、α、SP-1结合的顺式元件。凝胶迁移率分析表明，CREB、Ets-1、AP-2、α和SP-1均与PP2A-Aα基因启动子结合。体外诱变和报告基因活性检测表明，SP-1对PP2A-Aα基因启动子有负调控作用，而CREB、Ets-1和AP-2aα对PP2A-A基因启动子有正调控作用。芯片检测进一步证实上述转录因子均参与了PP2A-Aα基因启动子的调控。综上所述，我们的结果表明，多个转录因子调控PP2A-Aα基因。
Protein phosphatases-2A (PP-2A) is a major serine/threonine phosphatase and accounts for more than 50% serine/threonine phosphatase activity in eukaryotes. The holoenzyme of PP-2A consists of the scaffold A subunit, the catalytic C subunit and the regulatory B subunit. The scaffold subunits, PP2A-Aα/β, provide a platform for both C and B subunits to bind, thus playing a crucial role in providing specific PP-2A activity. Mutation of the two genes encoding PP2A-Aα/β leads to carcinogenesis and likely other human diseases. Regulation of these genes by various factors, both extracellular and intracellular, remains largely unknown. In the present study, we have conducted functional dissection of the promoter of the mouse PP2A-Aα gene. Our results demonstrate that the proximal promoter of the mouse PP2A-Aα gene contains numerous cis-elements for the binding of CREB, ETS-1, AP-2α, SP-1 besides the putative TFIIB binding site (BRE) and the downstream promoter element (DPE). Gel mobility shifting assays revealed that CREB, ETS-1, AP-2α, and SP-1 all bind to PP2A-Aα gene promoter. In vitro mutagenesis and reporter gene activity assays reveal that while SP-1 displays negative regulation, CREB, ETS-1 and AP-2Aα all positively regulate the promoter of the PP2A-Aα gene. ChIP assays further confirm that all the above transcription factors participate the regulation of PP2A-Aα gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aα gene.
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DOI：
10.1111/j.1432-1033.1992.tb16805.x
发表时间：
1992-04-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
LI, WC;RIDDIFORD, LM
通讯作者：
RIDDIFORD, LM
影响因子：
16.8
作者：
Chen, Yu;Xu, Yanhui;Shi, Yigong
通讯作者：
Shi, Yigong
影响因子：
8
作者：
Calin, GA;di Iasio, MG;Negrini, M
通讯作者：
Negrini, M
影响因子：
12.3
作者：
Eckert D;Buhl S;Weber S;Jäger R;Schorle H
通讯作者：
Schorle H
影响因子：
10.5
作者：
Burke, TW;Kadonaga, JT
通讯作者：
Kadonaga, JT