| First Author | Kurlishchuk Y | Year | 2024 |
| Journal | EMBO J | Volume | 43 |
| Issue | 20 | Pages | 4578-4603 |
| PubMed ID | 39210147 | Mgi Jnum | J:357547 |
| Mgi Id | MGI:7750218 | Doi | 10.1038/s44318-024-00188-0 |
| Citation | Kurlishchuk Y, et al. (2024) A non-canonical repressor function of JUN restrains YAP activity and liver cancer growth. EMBO J 43(20):4578-4603 |
| abstractText | Yes-associated protein (YAP) and its homolog, transcriptional coactivator with PDZ-binding motif (TAZ), are the main transcriptional downstream effectors of the Hippo pathway. Decreased Hippo pathway activity leads to nuclear translocation of YAP/TAZ where they interact with TEAD transcription factors to induce target gene expression. Unrestrained YAP/TAZ activity can lead to excessive growth and tumor formation in a short time, underscoring the evolutionary need for tight control of these two transcriptional coactivators. Here, we report that the AP-1 component JUN acts as specific repressor of YAP/TAZ at joint target sites to decrease YAP/TAZ activity. This function of JUN is independent of its heterodimeric AP-1 partner FOS and the canonical AP-1 function. Since expression of JUN is itself induced by YAP/TAZ, our work identifies a JUN-dependent negative feedback loop that buffers YAP/TAZ activity at joint genomic sites. This negative feedback loop gets disrupted in liver cancer to unlock the full oncogenic potential of YAP/TAZ. Our results thus demonstrate an additional layer of control for the interplay of YAP/TAZ and AP-1. |
