Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, Not Bax or Bak Academic Article uri icon


  • 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.


  • 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

publication date

  • February 9, 2007

has subject area