JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis

UMMS Affiliation

Howard Hughes Medical Institute and Program in Molecular Medicine



Document Type



*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.

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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


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Link to Article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID