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Updated: Aug 8, 2026

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Published on: June 6, 2017
Stress kinase MKK7: savior of cell cycle arrest and cellular senescence
Teiji Wada1, Josef M Penninger
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna. teiji.wada@imba.oeaw.ac.at
Abstract:
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signals to cell proliferation, cell cycle progression, cellular senescence, and apoptosis including recent unpublished data from our lab.
Insights
The stress-activated MKK4/MKK7-JNK-c-Jun pathway regulates cell proliferation, cell cycle, senescence, and apoptosis. This pathway links stress and developmental signals to critical cellular outcomes.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Stress Response Pathways
Background:
- The c-Jun N-terminal kinase (JNK/SAPK) signaling cascade is crucial for cellular processes like growth, differentiation, and apoptosis.
- Stress kinase MKK7 directly activates JNKs and influences cell cycle progression and senescence.
Purpose of the Study:
- To investigate the roles of MKK4 and c-Jun in the JNK pathway.
- To elucidate the MKK4/MKK7-JNK-c-Jun pathway's involvement in stress signaling and cellular fate decisions.
Main Methods:
- Exploration of molecules within the JNK pathway.
- Analysis of the functional roles of MKK4 and c-Jun.
- Integration of published and unpublished laboratory data.
Main Results:
- MKK4 and c-Jun were found to have roles similar to MKK7 in regulating cellular processes.
- The MKK4/MKK7-JNK-c-Jun pathway was identified as a key link between stress and developmental signals.
Conclusions:
- The MKK4/MKK7-JNK-c-Jun pathway is vital for controlling cell proliferation, cell cycle progression, cellular senescence, and apoptosis.
- This pathway integrates diverse signals to dictate fundamental cellular responses.
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