JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
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- 18 February 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (5) , 2432-2437
- https://doi.org/10.1073/pnas.0438011100
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 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.Keywords
This publication has 40 references indexed in Scilit:
- JNK Phosphorylation and Activation of BAD Couples the Stress-activated Signaling Pathway to the Cell Death MachineryJournal of Biological Chemistry, 2002
- FKHR-L1 can act as a critical effector of cell death induced by cytokine withdrawalThe Journal of cell biology, 2002
- BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and BakGenes & Development, 2001
- MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokinesGenes & Development, 2001
- Signal transduction by MAP kinases in T lymphocytesOncogene, 2001
- Downregulation of Bim, a Proapoptotic Relative of Bcl-2, Is a Pivotal Step in Cytokine-Initiated Survival Signaling in Murine Hematopoietic ProgenitorsMolecular and Cellular Biology, 2001
- Ordering the Cell Death PathwayJournal of Biological Chemistry, 1996
- Opposing Effects of ERK and JNK-p38 MAP Kinases on ApoptosisScience, 1995
- Pro-inflammatory Cytokines and Environmental Stress Cause p38 Mitogen-activated Protein Kinase Activation by Dual Phosphorylation on Tyrosine and ThreonineJournal of Biological Chemistry, 1995
- JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domainPublished by Elsevier ,1994