癌变
c-jun公司
癌症研究
癌基因
转录因子
磷酸化
肺癌
腺癌
肺
抄写(语言学)
化学
生物
基因
癌症
细胞生物学
医学
内科学
细胞周期
生物化学
遗传学
哲学
语言学
作者
E Josue Ruiz,Linxiang Lan,Markus E. Diefenbacher,Eva Madi Riising,Clive Da Costa,Atanu Chakraborty,Joerg D. Hoeck,Bradley Spencer‐Dene,Gavin Kelly,Jean‐Pierre David,Emma Nye,Julian Downward,Axel Behrens
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2021-07-08
卷期号:6 (13)
被引量:22
标识
DOI:10.1172/jci.insight.124985
摘要
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.
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