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Regulation of Dual specificity protein phosphatase‐2 (DUSP2) by hypoxia
Author(s) -
Lin ShihChieh,
Tsai ShawJenq
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1049.2
Subject(s) - microbiology and biotechnology , hypoxia (environmental) , protein phosphatase 1 , phosphatase , chemistry , kinase , phosphorylation , biochemistry , biology , organic chemistry , oxygen
Constitutive activation of MAP kinases was found in many cancers, and it's still an enigma that needs to be revealed. DUSP2 is a member of dual specificity protein phosphatase that regulates the activity of MAP kinases. Until now, the regulation of DUSP2 expression has not yet investigated. Hypoxia occurs in many solid tumors and has been shown to be a factor of increasing the MAP kinase activity. Therefore, we hypothesize that hypoxia‐induced MAP kinase activity may be mediated via deregulation of DUSP2 expression. We predicted a putative hypoxia response element (HRE) in the DUSP2 promoter region by using bioinformatic tool. Expression of DUSP2 was decreased by hypoxia treatment in HeLa cancer cells and normal endometrial stroma cells. Knockdown of HIF‐1α or HIF‐2αby siRNA reversed hypoxia‐mediated inhibition of DUSP2 expression. Promoter activity assay and site‐direct mutagenesis showed that predicted putative HRE was essential for downregulation of DUSP2 expression under hypoxic condition. Chromatin immunoprecipitation (ChIP) assay further demonstrated the binding of HIF‐1α to the HRE of DUSP2 promoter. ERK1/2, the downstream target of DUSP2, was activated by hypoxia and was inversely correlated with the expression of DUSP2. Taken together, we demonstrate that hypoxia downregulates the expression of DUSP2 thus enhances the activity of ERK1/2, which may be an important factor for cells to survive in hypoxic environment.