Publication Date:
2007-02-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willis, Simon N -- Fletcher, Jamie I -- Kaufmann, Thomas -- van Delft, Mark F -- Chen, Lin -- Czabotar, Peter E -- Ierino, Helen -- Lee, Erinna F -- Fairlie, W Douglas -- Bouillet, Philippe -- Strasser, Andreas -- Kluck, Ruth M -- Adams, Jerry M -- Huang, David C S -- CA43540/CA/NCI NIH HHS/ -- CA80188/CA/NCI NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):856-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289999" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Apoptosis Regulatory Proteins/chemistry/genetics/*metabolism
;
BH3 Interacting Domain Death Agonist Protein/chemistry/genetics/*metabolism
;
Cell Line
;
Cells, Cultured
;
Humans
;
Ligands
;
Membrane Proteins/chemistry/genetics/*metabolism
;
Mice
;
Mice, Knockout
;
Models, Biological
;
Mutation
;
Myeloid Cell Leukemia Sequence 1 Protein
;
Neoplasm Proteins/metabolism
;
Protein Structure, Tertiary
;
Proteins/metabolism
;
Proto-Oncogene Proteins/chemistry/genetics/*metabolism
;
Proto-Oncogene Proteins c-bcl-2/*metabolism
;
Tumor Suppressor Proteins/genetics/metabolism
;
bcl-2 Homologous Antagonist-Killer Protein/metabolism
;
bcl-2-Associated X Protein/chemistry/*metabolism
;
bcl-Associated Death Protein/metabolism
;
bcl-X Protein/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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