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Apoptosis and autophagy: Regulation of caspase‐9 by phosphorylation
Author(s) -
Allan Lindsey A.,
Clarke Paul R.
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07330.x
Subject(s) - apoptosome , microbiology and biotechnology , cytochrome c , caspase , apoptosis , phosphorylation , intrinsic apoptosis , biology , kinase , programmed cell death , mitochondrion , caspase 9 , caspase 2 , biochemistry
Cell death by the process of apoptosis plays important roles in development, tissue homeostasis, diseases and drug responses. The cysteine aspartyl protease caspase‐9 plays a central role in the mitochondrial or intrinsic apoptotic pathway that is engaged in response to many apoptotic stimuli. Caspase‐9 is activated in a large multimeric complex, the apoptosome, which is formed with apoptotic peptidase activating factor 1 (Apaf‐1) in response to the release of cytochrome c from mitochondria. Once activated, caspase‐9 cleaves and activates the effector caspases 3 and 7 to bring about apoptosis. This pathway is tightly regulated at multiple steps, including apoptosome formation and caspase‐9 activation. Recent work has shown that caspase‐9 is the direct target for regulatory phosphorylation by multiple protein kinases activated in response to extracellular growth/survival factors, osmotic stress or during mitosis. Here, we review these advances and discuss the possible roles of caspase‐9 phosphorylation in the regulation of apoptosis during development and in pathological states, including cancer.