Document Detail

Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim.
MedLine Citation:
PMID:  19079139     Owner:  NLM     Status:  MEDLINE    
Bcl-2 family members regulate apoptosis in response to cytokine withdrawal and a broad range of cytotoxic stimuli. Pro-apoptotic Bcl-2 family members Bax and Bak are essential for apoptosis triggered by interleukin-3 (IL-3) withdrawal in myeloid cells. The BH3-only protein Puma is critical for initiation of IL-3 withdrawal-induced apoptosis, because IL-3-deprived Puma(-/-) cells show increased capacity to form colonies when IL-3 is restored. To investigate the mechanisms of Puma-induced apoptosis and the interactions between Puma and other Bcl-2 family members, we expressed Puma under an inducible promoter in cells lacking one or more Bcl-2 family members. Puma rapidly induced apoptosis in cells lacking the BH3-only proteins, Bid and Bim. Puma expression resulted in activation of Bax, but Puma killing was not dependent on Bax or Bak alone as Puma readily induced apoptosis in cells lacking either of these proteins, but could not kill cells deficient for both. Puma co-immunoprecipitated with the anti-apoptotic Bcl-2 family members Bcl-x(L) and Mcl-1 but not with Bax or Bak. These data indicate that Puma functions, in the context of induced overexpression or IL-3 deprivation, primarily by binding and inactivating anti-apoptotic Bcl-2 family members.
A M Jabbour; J E Heraud; C P Daunt; T Kaufmann; J Sandow; L A O'Reilly; B A Callus; A Lopez; A Strasser; D L Vaux; P G Ekert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-12
Journal Detail:
Title:  Cell death and differentiation     Volume:  16     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-05-22     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  555-63     Citation Subset:  IM    
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MeSH Terms
Apoptosis / genetics,  physiology*
Apoptosis Regulatory Proteins / genetics,  metabolism*
BH3 Interacting Domain Death Agonist Protein / genetics,  metabolism*
Cell Line
Cell Survival / genetics
Cells, Cultured
Cytochromes c / metabolism
Fluorescent Antibody Technique
Interleukin-3 / deficiency,  physiology
Membrane Potential, Mitochondrial / genetics,  physiology
Membrane Proteins / genetics,  metabolism*
Mice, Inbred C57BL
Proto-Oncogene Proteins / genetics,  metabolism*
Tumor Suppressor Proteins / genetics,  metabolism*
bcl-2-Associated X Protein / genetics,  metabolism*
Grant Support
R01 CA043540/CA/NCI NIH HHS; R01 CA043540-22/CA/NCI NIH HHS
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BH3 Interacting Domain Death Agonist Protein; 0/Bax protein, mouse; 0/Bcl-2-like protein 11; 0/Bid protein, mouse; 0/Interleukin-3; 0/Membrane Proteins; 0/PUMA protein, mouse; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 0/bcl-2-Associated X Protein; 9007-43-6/Cytochromes c

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