| Autor: |
Xin Zhao, Yumei Fan, Jiayin Shen, Yifan Wu, Zhimin Yin |
| Zdroj: |
Molecules & Cells (Elsevier B.V); 2006, Vol. 21 Issue 3, p395-400, 6p |
| Abstrakt: |
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 ΔMEKK1- and etoposide-induced apoptosis, and inhibited procaspase- 3 activation and PARP cleavage. MEKK1- induced apoptosis requires both its kinase activity and proteolytic cleavage. ΔMEKK1 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 etoposideinduced cell apoptosis was mainly due to its ability to suppress MEKK1 kinase activity. The glutathioneconjugating 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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