c-Abl regulates Early Growth Response Protein (EGR1) in response to oxidative stress

Jeremy R. Stuart, Hidehiko Kawai, K. K C Tsai, Eric Y. Chuang, Zhi Min Yuan

研究成果: 雜誌貢獻文章同行評審

28 引文 斯高帕斯(Scopus)


c-Abl is a tyrosine kinase that can act as a regulator of cell growth and apoptosis in response to stress. Using cell lines expressing c-Abl in an inducible manner, we identified genes whose expression was regulated by c-Abl kinase activity. Microarray analysis indicated that Early Growth Response-1 (EGR1) gene expression is induced by c-Abl kinase activity, which was confirmed at the message and protein levels. Promoter mapping experiments revealed that c-Abl utilizes three distal serum response elements (SREs) in the EGR1 promoter, which are transactivated by mitogen/extracellular receptor kinase (MEK/ERK) signaling. PD 95089, a specific inhibitor of MEK/ERK signaling, attenuated c-Abl-mediated upregulation of EGR1 expression in a dose-dependent manner. Similar results were obtained by using a dominant-negative mutant of mitogen/extracellular kinase. Significantly, hydrogen peroxide-induced EGR1 expression appears to be mediated by c-Abl, as cells expressing dominant negative c-Abl, and c-Abl-/- murine embryonic fibroblasts, are completely defective in hydrogen peroxide-induced EGR1 expression. In addition, c-Abl-induced apoptosis is partially mitigated by EGR1 activity, as cells devoid of EGR1 expression undergo reduced rates of c-Abl-induced apoptosis. Together, these results indicate that c-Abl promotes the induction of EGR1 through the MEK/ERK pathway in regulating apoptotic response to oxidative stress.
頁(從 - 到)8085-8092
出版狀態已發佈 - 12月 8 2005

ASJC Scopus subject areas

  • 癌症研究
  • 遺傳學
  • 分子生物學


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