JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer.
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Embargo End Date
ICR Authors
Authors
Ruiz, EJ
Lan, L
Diefenbacher, ME
Riising, EM
Da Costa, C
Chakraborty, A
Hoeck, JD
Spencer-Dene, B
Kelly, G
David, J-P
Nye, E
Downward, J
Behrens, A
Lan, L
Diefenbacher, ME
Riising, EM
Da Costa, C
Chakraborty, A
Hoeck, JD
Spencer-Dene, B
Kelly, G
David, J-P
Nye, E
Downward, J
Behrens, A
Document Type
Journal Article
Date
2021-07-08
Date Accepted
2021-05-28
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.
Citation
JCI insight, 2021, 6 (13)
Source Title
Publisher
AMER SOC CLINICAL INVESTIGATION INC
ISSN
2379-3708
eISSN
2379-3708
Collections
Research Team
Lung Cancer Group
Lung Cancer Group
Lung Cancer Group