| First Author | Al Moussawi K | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 3 | Pages | 111503 |
| PubMed ID | 36261000 | Mgi Jnum | J:330598 |
| Mgi Id | MGI:7380212 | Doi | 10.1016/j.celrep.2022.111503 |
| Citation | Al Moussawi K, et al. (2022) Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis. Cell Rep 41(3):111503 |
| abstractText | Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator. |
