JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
- Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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Communicated by Richard A. Flavell, Yale University School of Medicine, New Haven, CT (received for review December 9, 2002)
Abstract
The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to environmental stress, including UV radiation. Gene disruption studies demonstrate that JNK is essential for UV-stimulated apoptosis mediated by the mitochondrial pathway by a Bax/Bak-dependent mechanism. Here, we demonstrate that JNK phosphorylates two members of the BH3-only subgroup of Bcl2-related proteins (Bim and Bmf) that are normally sequestered by binding to dynein and myosin V motor complexes. Phosphorylation by JNK causes release from the motor complexes. These proapoptotic BH3-only proteins therefore provide a molecular link between the JNK signal transduction pathway and the Bax/Bak-dependent mitochondrial apoptotic machinery.
Footnotes
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↵ * To whom correspondence should be addressed. E-mail: Roger.Davis{at}Umassmed.edu.
- Abbreviations:
- JNK,
- c-Jun NH2-terminal kinase;
- DLC,
- dynein light chain;
- MAPK,
- mitogen-activated protein kinase
- Copyright © 2003, The National Academy of Sciences
