JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer
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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 Axel BehrensAbstract
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.
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Journal JCI insight
Volume 6
Issue number 13
Pages e124985
Available online
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Publisher website (DOI) 10.1172/jci.insight.124985
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Europe PubMed Central 34236045
Pubmed 34236045
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