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PMID: 19380879 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members.

The Journal of cell biology ·Vol. 185 ·No. 2 ·2009-04-20 ·Pages 279-90

Gallenne T, Gautier F, Oliver L, Hervouet E, Noël B, Hickman JA, Geneste O, Cartron PF, Vallette FM, Manon S, Juin P

Abstract

It is still unclear whether the BH3-only protein Puma (p53 up-regulated modulator of apoptosis) can prime cells to death and render antiapoptotic BH3-binding Bcl-2 homologues necessary for survival through its ability to directly interact with proapoptotic Bax and activate it. In this study, we provide further evidence, using cell-free assays, that the BH3 domain of Puma binds Bax at an activation site that comprises the first helix of Bax. We also show that, in yeast, Puma interacts with Bax and triggers its killing activity when Bcl-2 homologues are absent but not when Bcl-xL is expressed. Finally, endogenous Puma is involved in the apoptotic response of human colorectal cancer cells to the Bcl-2/Bcl-xL inhibitor ABT-737, even in conditions where the expression of Mcl-1 is down-regulated. Thus, Puma is competent to trigger Bax activity by itself, thereby promoting cellular dependence on prosurvival Bcl-2 family members.

MeSH Terms
Apoptosis/physiology Apoptosis Regulatory Proteins/genetics,metabolism Biphenyl Compounds/metabolism Cell Line, Tumor Colorectal Neoplasms/metabolism Cyclin-Dependent Kinase Inhibitor p21/genetics,metabolism Gene Knockdown Techniques Humans Myeloid Cell Leukemia Sequence 1 Protein Nitrophenols/metabolism Piperazines/metabolism Protein Binding Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors,genetics,metabolism RNA Interference Sulfonamides/metabolism Yeasts/physiology bcl-2-Associated X Protein/antagonists & inhibitors,genetics,metabolism
Chemicals
ABT-737 Apoptosis Regulatory Proteins BBC3 protein, human Biphenyl Compounds Cyclin-Dependent Kinase Inhibitor p21 Myeloid Cell Leukemia Sequence 1 Protein Nitrophenols Piperazines Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Sulfonamides bcl-2-Associated X Protein
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Gallenne Tristan
Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 892, Département de Recherche en Cancérologie, F-44035 Nantes, Cedex 01, France.
Gautier Fabien
Oliver Lisa
Hervouet Eric
Noël Belinda
Hickman John A
Geneste Olivier
Cartron Pierre-François
Vallette François M
Manon Stephen
Juin Philippe
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200809153
Published
2009-04-20
Pages
279-90
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2700382
Subset
IM
Corrections
CommentIn
PMID: 19380876
External Links
PubMed source DOI: 10.1083/jcb.200809153 PMC Full Text View journal details
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