Article (Scientific journals)
Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1
Maurer, Ulrich; Charvet, Céline; Wagman, Allan et al.
2006In Molecular Cell, 21 (6), p. 749-760
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Keywords :
apoptosis, Mcl-1
Abstract :
[en] We investigated the role of glycogen synthase kinase-3 (GSK-3), which is inactivated by AKT, for its role in the regulation of apoptosis. Upon IL-3 withdrawal, protein levels of MCL-1 decreased but were sustained by pharmacological inhibition of GSK-3, which prevented cytochrome c release and apoptosis. MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). S159 phosphorylation of MCL-1 was induced by IL-3 withdrawal or PI3K inhibition and prevented by AKT or inhibition of GSK-3, and it led to increased ubiquitinylation and degradation of MCLA. A phosphorylation-site mutant (MCL-1(S159A)), expressed in IL-3-dependent cells, showed enhanced stability upon IL-3 withdrawal and conferred increased protection from apoptosis compared to wild-type MCL-1. The results demonstrate that the control of MCLA stability by GSK-3 is an important mechanism for the regulation of apoptosis by growth factors, PI3K, and AKT.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Maurer, Ulrich
Charvet, Céline
Wagman, Allan
Dejardin, Emmanuel ;  Université de Liège - ULiège > Virologie - Immunologie
Green, Douglas
Language :
English
Title :
Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1
Publication date :
17 March 2006
Journal title :
Molecular Cell
ISSN :
1097-2765
eISSN :
1097-4164
Publisher :
Cell Press, Cambridge, United Kingdom
Volume :
21
Issue :
6
Pages :
749-760
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 14 November 2011

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