Apoptosis and autophagy: regulation of caspase-9 by phosphorylation

TY - JOUR

T1 - Apoptosis and autophagy

T2 - regulation of caspase-9 by phosphorylation

AU - Allan, Lindsey A.

AU - Clarke, Paul R.

N1 - MEDLINE® is the source for the MeSH terms of this document.

PY - 2009/11

Y1 - 2009/11

N2 - 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.

AB - 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.

KW - apoptosis

KW - caspase

KW - mitosis

KW - phosphorylation

KW - protein kinase

KW - SPINDLE ASSEMBLY CHECKPOINT

KW - DEATH PROTEASE CASPASE-9

KW - CYTOCHROME-C

KW - CELL-DEATH

KW - HYPEROSMOTIC STRESS

KW - INHIBITORY SITE

KW - KINASE DYRK1A

KW - ACTIVATION

KW - PATHWAY

KW - APAF-1

UR - https://www.scopus.com/pages/publications/70349956567

U2 - 10.1111/j.1742-4658.2009.07330.x

DO - 10.1111/j.1742-4658.2009.07330.x

M3 - Article

C2 - 19788417

SN - 1742-464X

VL - 276

SP - 6063

EP - 6073

JO - FEBS Journal

JF - FEBS Journal

IS - 21

ER -