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Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak


Willis, SN; Fletcher, JI; Kaufmann, T; van Delft, MF; Chen, L; Czabotar, PE; Ierino, H; Lee, EF; Fairlie, WD; Bouillet, P; Strasser, A; Kluck, RM; Adams, JM; Huang, DCS
2007-02-09
SCIENCE
Journal Article
315
5813
856-859
A central issue in the regulation of apoptosis by the Bcl-2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell-death mediators Bax and Bak, or whether they can act indirectly, by engaging their pro-survival Bcl-2-like relatives. Contrary to the direct-activation model, we show that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma. Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak.
AMER ASSOC ADVANCEMENT SCIENCE
BH3-ONLY PROTEINS; MITOCHONDRIAL-MEMBRANE; FAMILY-MEMBERS; CELL-DEATH; X-L; BIM; PUMA; RESPONSES; DOMAINS; HELIX
10.1126/science.1133289
Refer to copyright notice on published article.

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Creation Date 2007-02-09 12:00:00