1. JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer
- Author
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E. Josue Ruiz, Linxiang Lan, Markus Elmar Diefenbacher, Eva Madi Riising, Clive Da Costa, Atanu Chakraborty, Joerg D. Hoeck, Bradley Spencer-Dene, Gavin Kelly, Jean-Pierre David, Emma Nye, Julian Downward, and Axel Behrens
- Subjects
Cell biology ,Oncology ,Medicine - Abstract
The AP-1 transcription factor c-Jun is required for Ras-driven tumorigenesis in many tissues and is considered as a classical proto-oncogene. To determine the requirement for c-Jun in a mouse model of K-RasG12D–induced lung adenocarcinoma, we inducibly deleted c-Jun in the adult lung. Surprisingly, we found that inactivation of c-Jun, or mutation of its JNK phosphorylation sites, actually increased lung tumor burden. Mechanistically, we found that protein levels of the Jun family member JunD were increased in the absence of c-Jun. In c-Jun–deficient cells, JunD phosphorylation was increased, and expression of a dominant-active JNKK2-JNK1 transgene further increased lung tumor formation. Strikingly, deletion of JunD completely abolished Ras-driven lung tumorigenesis. This work identifies JunD, not c-Jun, as the crucial substrate of JNK signaling and oncogene required for Ras-induced lung cancer.
- Published
- 2021
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