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 journalArticle

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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  • Cite this

    Liu, J., Ji, W., Sun, S., Zhang, L., Chen, H. G., Mao, Y., Liu, L., Zhang, X., Gong, L., Deng, M., Chen, L., Han, W. J., Chen, P. C., Hu, W. F., Hu, X., Liu, J., Woodward, Z., Liu, W. B., Xiao, Y. M., ... Li, D. W. C. (2012). The PP2A-Aβ gene is regulated by multiple transcriptional factors including Ets-1, SP1/SP3, and RXRα/β. Current molecular medicine, 12(8), 982-994. https://doi.org/10.2174/156652412802480916