Title
Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis
UMMS Affiliation
Program in Molecular Medicine
Publication Date
5-13-2009
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
Abstract
Mcl-1 is a member of the Bcl2-related protein family that is a critical mediator of cell survival. Exposure of cells to stress causes inhibition of Mcl-1 mRNA translation and rapid destruction of Mcl-1 protein by proteasomal degradation mediated by a phosphodegron created by glycogen synthase kinase 3 (GSK3) phosphorylation of Mcl-1. Here we demonstrate that prior phosphorylation of Mcl-1 by the c-Jun N-terminal protein kinase (JNK) is essential for Mcl-1 phosphorylation by GSK3. Stress-induced Mcl-1 degradation therefore requires the coordinated activity of JNK and GSK3. Together, these data establish that Mcl-1 functions as a site of signal integration between the proapoptotic activity of JNK and the prosurvival activity of the AKT pathway that inhibits GSK3.
Rights and Permissions
Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
DOI of Published Version
10.1128/MCB.00279-09
Source
Mol Cell Biol. 2009 Jul;29(14):3845-52. Epub 2009 May 11. Link to article on publisher's site
Journal/Book/Conference Title
Molecular and cellular biology
Related Resources
PubMed ID
19433446
Repository Citation
Morel, Caroline; Carlson, Scott M.; White, Forest M.; and Davis, Roger J., "Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis" (2009). Open Access Articles. 2179.
https://escholarship.umassmed.edu/oapubs/2179
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Biochemistry Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Molecular Biology Commons