| Autor: |
Ding HF; Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, Massachusetts 02115, USA., Lin YL, McGill G, Juo P, Zhu H, Blenis J, Yuan J, Fisher DE |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2000 Dec 08; Vol. 275 (49), pp. 38905-11. |
| DOI: |
10.1074/jbc.M004714200 |
| Abstrakt: |
p53's dual regulation of arrest versus apoptosis may underlie tumor-selective effects of anti-cancer therapy. p53's apoptotic effect has been suggested to involve both transcription-dependent and -independent mechanisms. It is shown here that caspase-8 is activated early in cells undergoing p53-mediated apoptosis and in S100 cell-free extracts that recapitulate transcription-independent apoptosis. Depletion or inactivation of caspase-8 either in cells or cell-free extracts completely prevents this transcription-independent apoptosis and significantly attenuates overall death induced by wild-type p53. Importantly, caspase-8 activation appears to be independent of FADD, and caspase-8 is found in a novel 600-kDa complex following p53 activation. These findings highlight the roles of both transcription-dependent and -independent apoptosis by p53 and identify an essential role for caspase-8 in the transcription-independent pathway. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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