JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
Howard Hughes Medical Institute and Program in Molecular Medicine
*Adaptor Proteins, Signal Transducing; *Apoptosis; Apoptosis Regulatory Proteins; Carrier Proteins; Cell Line; DNA Mutational Analysis; DNA, Complementary; Fibroblasts; Humans; *Membrane Proteins; Mitochondria; Models, Biological; Neurons; Phosphorylation; Plasmids; Protein Binding; Protein Isoforms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Threonine; bcl-2-Associated X Protein
Life Sciences | Medicine and Health Sciences
The c-Jun NH(2)-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.
Rights and Permissions
Citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2432-7. Epub 2003 Feb 18. Link to article on publisher's site
DOI of Published Version
Proceedings of the National Academy of Sciences of the United States of America
Lei, Kui and Davis, Roger J., "JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis" (2003). Open Access Articles. 1773.