作者
Pawel K Mazur, Nicolas Reynoird, Purvesh Khatri, Pascal WTC Jansen, Alex W Wilkinson, Shichong Liu, Olena Barbash, Glenn S Van Aller, Michael Huddleston, Dashyant Dhanak, Peter J Tummino, Ryan G Kruger, Benjamin A Garcia, Atul J Butte, Michiel Vermeulen, Julien Sage, Or Gozani
发表日期
2014/6/12
期刊
Nature
卷号
510
期号
7504
页码范围
283-287
出版商
Nature Publishing Group UK
简介
Deregulation of lysine methylation signalling has emerged as a common aetiological factor in cancer pathogenesis, with inhibitors of several histone lysine methyltransferases (KMTs) being developed as chemotherapeutics. The largely cytoplasmic KMT SMYD3 (SET and MYND domain containing protein 3) is overexpressed in numerous human tumours,,. However, the molecular mechanism by which SMYD3 regulates cancer pathways and its relationship to tumorigenesis in vivo are largely unknown. Here we show that methylation of MAP3K2 by SMYD3 increases MAP kinase signalling and promotes the formation of Ras-driven carcinomas. Using mouse models for pancreatic ductal adenocarcinoma and lung adenocarcinoma, we found that abrogating SMYD3 catalytic activity inhibits tumour development in response to oncogenic Ras. We used protein array technology to identify the MAP3K2 kinase as a target …
学术搜索中的文章
PK Mazur, N Reynoird, P Khatri, PWTC Jansen… - Nature, 2014