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Abstract:
Accumulated evidences showed that Akt is a major cell survival pathway and plays an important role in malignant transformation and chemoresistance. However, the underlying mechanisms have not been well documented. We demonstrated that Akt protects stress-induced programmed cell death by inhibition of stress kinase JNK/p38 through activation of NFkB pathway. Further, we have shown that human cancer cells expressing constitutively active AKT2 resist to cisplatin through inhibition of cisplatin-induced ASK1 (apoptosis signal-regulating kinase 1) activation. AKT2 phosphorylation of ASK1 led to abrogation of cisplatin-induced JNK/p38 activation and Bax conformational changes. MST1, one member of STE20 like kinase, has been shown to induce apoptosis through its cleavage, activation and nuclear translocation. We have recently observed that AKT2 inhibits MST1-induced apoptosis by phosphorylatiion of MST1 at Thr-120.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual summary rept. 1 Jun 2002-31 May 2003 |
| Pages: |
29 |
| Report Date: |
JUN 2003 |
| Contract Number: |
DAMD17-01-1-0397 |
| Report Number: |
A599714 |
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