Back to Search
Start Over
JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer
- Source :
- JCI Insight
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
Abstract
- 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.
- Subjects :
- Lung Neoplasms
Carcinogenesis
MAP Kinase Signaling System
Proto-Oncogene Proteins c-jun
Transgene
Adenocarcinoma of Lung
MAP Kinase Kinase 7
Biology
medicine.disease_cause
Mice
Genes, jun
medicine
Animals
Gene Silencing
Phosphorylation
Lung cancer
Transcription factor
integumentary system
Oncogene
c-jun
Cell Biology
General Medicine
medicine.disease
Gene Expression Regulation, Neoplastic
Transcription Factor AP-1
AP-1 transcription factor
Oncology
ras Proteins
Cancer research
Research Article
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....04f2d01a568224a2eabb7f4301d7d6cc