Transcriptional regulation of PP2A-Aα is mediated by multiple factors including AP-2α, CREB, ETS-1, and SP-1

He Ge Chen, Wen Jun Han, Mi Deng, Jichao Qin, Dan Yuan, Jin Ping Liu, Ling Xiao, Lili Gong, Songping Liang, Jian Zhang, Yun Liu, David Wan Cheng Li

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere7019
JournalPloS one
Volume4
Issue number9
DOIs
StatePublished - Sep 14 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Chen, H. G., Han, W. J., Deng, M., Qin, J., Yuan, D., Liu, J. P., Xiao, L., Gong, L., Liang, S., Zhang, J., Liu, Y., & Li, D. W. C. (2009). Transcriptional regulation of PP2A-Aα is mediated by multiple factors including AP-2α, CREB, ETS-1, and SP-1. PloS one, 4(9), [e7019]. https://doi.org/10.1371/journal.pone.0007019