Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway.
The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.
Tournier
C
C
Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry & Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Hess
P
P
Yang
D D
DD
Xu
J
J
Turner
T K
TK
Nimnual
A
A
Bar-Sagi
D
D
Jones
S N
SN
Flavell
R A
RA
Davis
R J
RJ
D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism*; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005347:Fibroblasts; D018390:Gene Targeting; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D016328:NF-kappa B; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D008741:Methyl Methanesulfonate; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases