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Biochim Biophys Acta. 2012 Jan;1824(1):113-22. doi: 10.1016/j.bbapap.2011.06.005. Epub 2011 Jun 16.

Proliferative versus apoptotic functions of caspase-8 Hetero or homo: the caspase-8 dimer controls cell fate.

Author information

1
Program of Apoptosis and Cell Death Research, Sanford-Burnham Institute, La Jolla, CA 92037, USA. b.j.vanraam@gmail.com

Abstract

Caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. It has become increasingly clear that the heterodimer of caspase-8 with the long isoform of cellular FLIP (FLIP(L)) fulfills these pro-survival functions of caspase-8. FLIP(L), a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIP(L) heterodimer has a restricted substrate repertoire and does not induce apoptosis. In essence, caspase-8 heterodimerized with FLIP(L) prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis. This review discusses the latest insights in caspase-8 homo- versus heterodimerization and the implication this has for cellular death or survival. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

PMID:
21704196
PMCID:
PMC3993904
DOI:
10.1016/j.bbapap.2011.06.005
[Indexed for MEDLINE]
Free PMC Article

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