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 W Li

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

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Genes
promoter regions
Protein Phosphatase 2
phosphoprotein phosphatase
Transcription Factor AP-1
genes
Assays
Phosphoprotein Phosphatases
threonine
Scaffolds
serine
assays
Transcription Factors
transcription factors
Transcription Factor TFIIB
Dissection
Mutagenesis
Holoenzymes
Gene encoding
mice

ASJC Scopus subject areas

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

Cite this

Transcriptional regulation of PP2A-Aα is mediated by multiple factors including AP-2α, CREB, ETS-1, and SP-1. / Chen, He Ge; Han, Wen Jun; Deng, Mi; Qin, Jichao; Yuan, Dan; Liu, Jin Ping; Xiao, Ling; Gong, Lili; Liang, Songping; Zhang, Jian; Liu, Yun; Li, David W.

In: PloS one, Vol. 4, No. 9, e7019, 14.09.2009.

Research output: Contribution to journalArticle

Chen, HG, Han, WJ, Deng, M, Qin, J, Yuan, D, Liu, JP, Xiao, L, Gong, L, Liang, S, Zhang, J, Liu, Y & Li, DW 2009, 'Transcriptional regulation of PP2A-Aα is mediated by multiple factors including AP-2α, CREB, ETS-1, and SP-1', PloS one, vol. 4, no. 9, e7019. https://doi.org/10.1371/journal.pone.0007019
Chen, He Ge ; Han, Wen Jun ; Deng, Mi ; Qin, Jichao ; Yuan, Dan ; Liu, Jin Ping ; Xiao, Ling ; Gong, Lili ; Liang, Songping ; Zhang, Jian ; Liu, Yun ; Li, David W. / Transcriptional regulation of PP2A-Aα is mediated by multiple factors including AP-2α, CREB, ETS-1, and SP-1. In: PloS one. 2009 ; Vol. 4, No. 9.
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AU - Qin, Jichao

AU - Yuan, Dan

AU - Liu, Jin Ping

AU - Xiao, Ling

AU - Gong, Lili

AU - Liang, Songping

AU - Zhang, Jian

AU - Liu, Yun

AU - Li, David W

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AB - 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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