Abstract:
:Tight control of apoptosis is required for proper development and maintenance of homeostasis in multicellular organisms. Cells can protect themselves from potentially lethal stimuli by expressing antiapoptotic factors, such as inhibitors of apoptosis, FLICE (caspase 8)-inhibitory proteins, and members of the Bcl2 family. Here, we describe a mechanism that allows cells to survive once executioner caspases have been activated. This mechanism relies on the partial cleavage of RasGAP by caspase 3 into an amino-terminal fragment called fragment N. Generation of this fragment leads to the activation of the antiapoptotic Akt kinase, preventing further amplification of caspase activity. Partial cleavage of RasGAP is required for cell survival under stress conditions because cells expressing an uncleavable RasGAP mutant cannot activate Akt, cannot prevent amplification of caspase 3 activity, and eventually undergo apoptosis. Executioner caspases therefore control the extent of their own activation by a feedback regulatory mechanism initiated by the partial cleavage of RasGAP that is crucial for cell survival under adverse conditions.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Yang JY,Michod D,Walicki J,Murphy BM,Kasibhatla S,Martin SJ,Widmann Cdoi
10.1128/MCB.24.23.10425-10436.2004subject
Has Abstractpub_date
2004-12-01 00:00:00pages
10425-36issue
23eissn
0270-7306issn
1098-5549pii
24/23/10425journal_volume
24pub_type
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