Back to Search
Start Over
Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis
- Source :
- Cell Reports, 41, 3, pp. 1-28, Cell Reports, 41, 1-28
- Publication Year :
- 2022
-
Abstract
- 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.
- Subjects :
- Inflammation
p63
AP1/JNK
skin cancer
Settore BIO/11
MAP Kinase Kinase 4
iASPP
Intracellular Signaling Peptides and Proteins
inflammation-driven tumorigenesis
General Biochemistry, Genetics and Molecular Biology
Repressor Proteins
Transcription Factor AP-1
Mice
Cell Transformation, Neoplastic
target selective transcription
Tumor Microenvironment
Animals
Tumor Suppressor Protein p53
Molecular Developmental Biology
CP: Cancer
RAS
Subjects
Details
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- Cell Reports, 41, 3, pp. 1-28, Cell Reports, 41, 1-28
- Accession number :
- edsair.doi.dedup.....d8be9fc25e494c45f5112c6ec80f3c91