Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak
Simon N Willis, Jamie I Fletcher, Thomas Kaufmann, Mark F van Delft, Lin Chen, Peter E Czabotar, Helen Ierino, Erinna F Lee, W Douglas Fairlie, Philippe Bouillet, Andreas Strasser, Ruth M Kluck, Jerry M Adams, David CS Huang
Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2007
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.
Awarded by NCI NIH HHS
Awarded by NATIONAL CANCER INSTITUTE