Stress kinase MKK7: savior of cell cycle arrest and cellular senescence.
The c-Jun N-terminal kinase (JNK/SAPK) signaling cascade controls a spectrum of cellular processes, including cell growth, differentiation, transformation, and apoptosis. We recently demonstrated that stress kinase MKK7, a direct activator of JNKs, couples stress signaling to G2/M cell cycle progression, CDC2 expression, and cellular senescence. We further explored other molecules involved in JNK pathway and found that both MKK4, another direct activator of JNK, and c-Jun, a direct substrate of JNK, have similar roles to MKK7. Here we discuss the importance of the MKK4/MKK7-JNK-c-Jun pathway linking stress and developmental signals to cell proliferation, cell cycle progression, cellular senescence, and apoptosis including recent unpublished data from our lab.
Wada
Teiji
T
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna. teiji.wada@imba.oeaw.ac.at
Penninger
Josef M
JM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000196:embryology / Q000254:growth & development; D048688:MAP Kinase Kinase 7; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D016203:CDC2 Protein Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482570:Map2k7 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases