Abstract
The c-Jun N-terminal kinases (JNKs) are activated by a variety of stress inducing agents and are thought to regulate apoptosis in a cell type and signal-specific manner. We have used fibroblasts lacking JNK1 or JNK2 to define their roles in response to different stress signals. Lack of JNK1 results in reduced c-Jun phosphorylation and resistance to UV-induced cell death. JNK2 deficient cells show increased sensitivity to UV irradiation which correlates with elevated and sustained phosphorylation of JNK1 and c-Jun. On the contrary, both Jnk1−/− and Jnk2−/− cells were more sensitive to tumor necrosis factor - alpha (TNF-α) and sorbitol-induced cell death. Treatment of Jnk1−/− cells with these reagents resulted in reduced JNK activity and a concomitant reduction of c-Jun phosphorylation, suggesting that phosphorylation of c-Jun does not influence TNF-α and sorbitol-induced apoptosis in fibroblasts. Moreover, both JNK1 and JNK2 appear to negatively regulate apoptosis independent of c-Jun phosphorylation. These data provide genetic evidence that although the JNK pathway is activated by a plethora of signals, it is required only for the induction of UV-induced cell death in a c-Jun phosphorylation-dependent manner, but not for TNF-α and sorbitol-induced apoptosis.
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Change history
31 May 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41388-023-02719-1
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Acknowledgements
We thank Dr A Behrens for critical reading of the manuscript. The IMP is supported by Boehringer Ingelheim. Part of this work was supported by the Austrian Federal Ministry of Science, Transport and the Arts.
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Hochedlinger, K., Wagner, E. & Sabapathy, K. Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis. Oncogene 21, 2441–2445 (2002). https://doi.org/10.1038/sj.onc.1205348
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DOI: https://doi.org/10.1038/sj.onc.1205348
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