JNK regulates the release of proapoptotic mitochondrial factors in reovirus-infected cells.
Reovirus-induced apoptosis is associated with activation of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and the JNK-associated transcription factor c-Jun. Here we show that reovirus-induced apoptosis and activation of caspase 3 are inhibited in cells deficient in MEK kinase 1, an upstream activator of JNK in reovirus-infected cells. Inhibition of JNK activity following reovirus infection delays the release of proapoptotic mitochondrial factors and the subsequent onset of apoptosis. In contrast, reovirus-induced apoptosis is not blocked by infection with adenovirus expressing dominant-negative c-Jun, and c-Jun activation does not correlate with apoptosis in reovirus-infected cells. This is the first report demonstrating that JNK is associated with regulation of mitochondrial pathways of apoptosis following viral infection.
Clarke
Penny
P
Dept. of Neurology (B 182), University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262, USA. penny.clarke@uchsc.edu
Meintzer
Suzanne M
SM
Wang
Yibing
Y
Moffitt
Lisa A
LA
Richardson-Burns
Sarah M
SM
Johnson
Gary L
GL
Tyler
Kenneth L
KL
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D048728:MAP Kinase Kinase Kinase 1 / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D012087:Reoviridae / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1