Apoptosis and autophagy

regulation of caspase-9 by phosphorylation

Lindsey A. Allan, Paul R. Clarke

    Research output: Contribution to journalArticle

    137 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)6063-6073
    Number of pages11
    JournalFEBS Journal
    Volume276
    Issue number21
    DOIs
    Publication statusPublished - Nov 2009

    Keywords

    • apoptosis
    • caspase
    • mitosis
    • phosphorylation
    • protein kinase
    • SPINDLE ASSEMBLY CHECKPOINT
    • DEATH PROTEASE CASPASE-9
    • CYTOCHROME-C
    • CELL-DEATH
    • HYPEROSMOTIC STRESS
    • INHIBITORY SITE
    • KINASE DYRK1A
    • ACTIVATION
    • PATHWAY
    • APAF-1

    Cite this

    Allan, Lindsey A. ; Clarke, Paul R. / Apoptosis and autophagy : regulation of caspase-9 by phosphorylation. In: FEBS Journal. 2009 ; Vol. 276, No. 21. pp. 6063-6073.
    @article{030f3936124345a48e00bd4e833641ca,
    title = "Apoptosis and autophagy: regulation of caspase-9 by phosphorylation",
    abstract = "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.",
    keywords = "apoptosis, caspase, mitosis, phosphorylation, protein kinase, SPINDLE ASSEMBLY CHECKPOINT, DEATH PROTEASE CASPASE-9, CYTOCHROME-C, CELL-DEATH, HYPEROSMOTIC STRESS, INHIBITORY SITE, KINASE DYRK1A, ACTIVATION, PATHWAY, APAF-1",
    author = "Allan, {Lindsey A.} and Clarke, {Paul R.}",
    note = "MEDLINE{\circledR} is the source for the MeSH terms of this document.",
    year = "2009",
    month = "11",
    doi = "10.1111/j.1742-4658.2009.07330.x",
    language = "English",
    volume = "276",
    pages = "6063--6073",
    journal = "FEBS Journal",
    issn = "1742-464X",
    publisher = "Wiley",
    number = "21",

    }

    Apoptosis and autophagy : regulation of caspase-9 by phosphorylation. / Allan, Lindsey A.; Clarke, Paul R.

    In: FEBS Journal, Vol. 276, No. 21, 11.2009, p. 6063-6073.

    Research output: Contribution to journalArticle

    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 - http://www.scopus.com/inward/record.url?scp=70349956567&partnerID=8YFLogxK

    U2 - 10.1111/j.1742-4658.2009.07330.x

    DO - 10.1111/j.1742-4658.2009.07330.x

    M3 - Article

    VL - 276

    SP - 6063

    EP - 6073

    JO - FEBS Journal

    JF - FEBS Journal

    SN - 1742-464X

    IS - 21

    ER -