Michael Wei, MD, PhD

Publication Details

  • BCL-2, BCL-X-L sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis MOLECULAR CELL Cheng, E. H., Wei, M. C., Weiler, S., Flavell, R. A., Mak, T. W., LINDSTEN, T., Korsmeyer, S. J. 2001; 8 (3): 705-711

    Abstract:

    Critical issues in apoptosis include the importance of caspases versus organelle dysfunction, dominance of anti- versus proapoptotic BCL-2 members, and whether commitment occurs upstream or downstream of mitochondria. Here, we show cells deficient for the downstream effectors Apaf-1, Caspase-9, or Caspase-3 display only transient protection from "BH3 domain-only" molecules and die a caspase-independent death by mitochondrial dysfunction. Cells with an upstream defect, lacking "multidomain" BAX, BAK demonstrate long-term resistance to all BH3 domain-only members, including BAD, BIM, and NOXA. Comparison of wild-type versus mutant BCL-2, BCL-X(L) indicates these antiapoptotics sequester BH3 domain-only molecules in stable mitochondrial complexes, preventing the activation of BAX, BAK. Thus, in mammals, BH3 domain-only molecules activate multidomain proapoptotic members to trigger a mitochondrial pathway, which both releases cytochrome c to activate caspases and initiates caspase-independent mitochondrial dysfunction.

    View details for Web of Science ID 000171251500024

    View details for PubMedID 11583631

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