JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis.
Journal:
Proc. Natl. Acad. Sci. U.S.A. 2003 MarAuthors:
Lei K, Davis RJ
Abstract
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 b
...[more]y 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.[less]
Mesh Headings:
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