Isolation and characterization of DUSP11, a novel p53 target gene

Greta Caprara, Raffaella Zamponi, Marina Melixetian, Kristian Helin

Research output: Contribution to journalArticlepeer-review

Abstract

p53 regulates the expression of genes involved in cell cycle control, apoptosis and DNA damage repair. Here we demonstrate that DUSP11 (dual specificity phosphatase 11), a member of the protein tyrosine phosphatase family that binds to RNA-RNP complexes and RNA splicing factors, is a p53 target gene. Consistent with this, the expression of DUSP11 is induced in a p53-dependent manner after treatment with DNA damaging agents. Chromatin immunoprecipitation analysis showed that p53 binds to 2 putative p53 DNA binding sites in the promoter region of DUSP11. Colony formation and proliferation assays demonstrated that the ectopic expression of wild-type, but not catalytical inactive, DUSP11 leads to growth arrest. Furthermore inhibition of DUSP11 expression by shRNA increases the proliferation of normal and DNA damaged cells in tissue culture. Finally we show that the splicing factor SAM68 (Src-associated protein in mitotic cells) binds to DUSP11 in vitro and in vivo. Taken together these results suggest that DUSP11 contributes to p53-dependent inhibition of cell proliferation and that it might be involved in regulating RNA splicing through SAM68.

Original languageEnglish
Pages (from-to)2158-2170
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number8 B
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Cellular proliferation
  • DNA damage
  • P53
  • RNA splicing

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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