Life-or-death decisions by the Bcl-2 protein family.
In response to intracellular damage and certain physiological cues, cells enter the suicide program termed apoptosis, executed by proteases called caspases. Commitment to apoptosis is typically governed by opposing factions of the Bcl-2 family of cytoplasmic proteins. Initiation of the proteolytic cascade requires assembly of certain caspase precursors on a scaffold protein, and the Bcl-2 family determines whether this complex can form. Its pro-survival members can act by sequestering the scaffold protein and/or by preventing the release of apoptogenic molecules from organelles such as mitochondria. Pro-apoptotic family members act as sentinels for cellular damage: cytotoxic signals induce their translocation to the organelles where they bind to their pro-survival relatives, promote organelle damage and trigger apoptosis.
Adams
J M
JM
The Walter and Eliza Hall Institute of Medical Research, P O Royal Melbourne Hospital, 3050, Melbourne, Australia. adams@wehi.edu.au
Cory
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D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015801:Helminth Proteins; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D015801:Helminth Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans