Molecules and Cells

  • 제21권3호
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  • Pages.395-400
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  • 2006
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

Human Glutathione S-Transferase P1 Suppresses MEKK1-mediated Apoptosis by Regulating MEKK1 Kinase Activity in HEK293 Cells

  • Zhao, Xin (Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University) ;
  • Fan, Yumei (Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University) ;
  • Shen, Jiayin (Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University) ;
  • Wu, Yifan (Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University) ;
  • Yin, Zhimin (Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University)
  • 투고 : 2006.02.15
  • 심사 : 2006.04.21
  • 발행 : 2006.06.30
⟨ 이전 논문 다음 논문 ⟩

초록

Glutathione S-transferase P1 (GSTP1) plays an important role in detoxification and the metabolism of xenobiotics. Here we show that GSTP1 also regulates the MEKK1-MKK7 signaling pathway. Over-expression of GSTP1 in HEK293 cells inhibited both ${\Delta}MEKK1$- and etoposide-induced apoptosis, and inhibited procaspase-3 activation and PARP cleavage. MEKK1- induced apoptosis requires both its kinase activity and proteolytic cleavage. ${\Delta}MEKK1$ activity was inhibited by over-expression of GSTP1 in vivo and MEKK1 kinase activity was also inhibited by GSTP1 in vitro when assayed with bacterially-expressed MKK7(KM) protein as substrate. GSTP1 inhibition of etoposide-induced cell apoptosis was mainly due to its ability to suppress MEKK1 kinase activity. The glutathione-conjugating activity of GSTP1 was essential for the above effects. These findings provide insight into the mechanism by which GSTP1 protects cells from genotoxin-induced apoptosis.

키워드

과제정보

연구 과제 주관 기관 : National Nature Science Foundation of China

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