Document Detail


Caspase-3 triggers a TPCK-sensitive protease pathway leading to degradation of the BH3-only protein puma.
MedLine Citation:
PMID:  20640889     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The protein Puma (p53-upregulated modulator of apoptosis) belongs to the BH3-only group of the Bcl-2 family and is a major regulator of apoptosis. Although the transcriptional regulation of Puma is clearly established, little is known about the regulation of its expression at the protein levels. We show here that various signals--including the cytokine TGFβ, the death effector TRAIL or chemical drugs such as anisomycin--downregulate Puma protein levels via a novel pathway based on the sequential activation of caspase-3 and a protease inhibited by the serpase inhibitor N-tosyl-L-phenylalanine chloromethyl ketone. This pathway is specific for Puma because (1) the levels of other BH3-only proteins, such as Bim and Noxa were not modified by these stimuli and (2) this caspase-mediated degradation was dependent on both the BH3 and C-terminal domains of Puma. Our data also show that Puma is regulated during the caspase-3-dependent differentiation of murine embryonic stem cells and suggest that this pathway may be relevant and important during caspase-mediated cell differentiation not associated with apoptosis.
Authors:
Abbas Hadji; Cyril Clybouw; Marie-Thérèse Auffredou; Catherine Alexia; Konstantinos Poalas; Aude Burlion; Olivier Feraud; Gérald Leca; Aimé Vazquez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  15     ISSN:  1573-675X     ISO Abbreviation:  Apoptosis     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1529-39     Citation Subset:  IM    
Affiliation:
INSERM U.1014, Batiment Lavoisier, Hôpital Paul Brousse, 14 Avenue Paul Vaillant Couturier, 94807 Villejuif, France.
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