The PP2A-Aβ gene is regulated by multiple transcriptional factors including Ets-1, SP1/SP3, and RXRα/β

J. Liu, W. Ji, S. Sun, L. Zhang, H. G. Chen, Y. Mao, L. Liu, X. Zhang, L. Gong, M. Deng, L. Chen, W. J. Han, P. C. Chen, W. F. Hu, X. Hu, J. Liu, Z. Woodward, W. B. Liu, Y. M. Xiao, S. P. LiangY. Liu, Shao Jun Liu, David Wan Cheng Li

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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-Aα/β, 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-Aα and PP2A-Aβ lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aβ gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/β, are present in the proximal promoter of the mouse PP2A-Aβ gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/β all bind to PP2A-Aβ gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/β positively regulate the promoter of the PP2A-Aβ gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/β and the luciferase reporter gene driven by PP2A-Aβ promoter further confirm their control over the PP2A-Aβ promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/β can all bind to the PP2A-Aβ gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aβ gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aβ display distinct expression levels.

Original languageEnglish (US)
Pages (from-to)982-994
Number of pages13
JournalCurrent Molecular Medicine
Volume12
Issue number8
DOIs
StatePublished - 2012

Keywords

  • Cancer
  • Cataract
  • Dephosphorylation
  • Ets
  • Gene regulation
  • Lens
  • PP-2A
  • PP2A-Aβ
  • Protein phosphorylation
  • RXRa/β
  • Retina
  • SP1
  • SP3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

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