JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancerMore about Open Access at the Crick
Authors listJosue 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 Axel Behrens
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.
Journal JCI insight
Issue number 13