| First Author | Ruiz EJ | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 13 | PubMed ID | 34236045 |
| Mgi Jnum | J:312882 | Mgi Id | MGI:6793007 |
| Doi | 10.1172/jci.insight.124985 | Citation | Ruiz EJ, et al. (2021) JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer. JCI Insight 6(13) |
| abstractText | 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. |
