Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, Not Bax or Bak-Reference-Cited by-同舟云学术

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

Published:2007-02-09 Issue:5813 Volume:315 Page:856-859
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Willis Simon N.¹²,Fletcher Jamie I.¹²,Kaufmann Thomas¹²,van Delft Mark F.¹²,Chen Lin¹²,Czabotar Peter E.¹²,Ierino Helen¹²,Lee Erinna F.¹²,Fairlie W. Douglas¹²,Bouillet Philippe¹²,Strasser Andreas¹²,Kluck Ruth M.¹²,Adams Jerry M.¹²,Huang David C. S.¹²

Affiliation:

1. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.

2. Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference26 articles.

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