期刊
CELL REPORTS
卷 2, 期 5, 页码 1233-1243出版社
CELL PRESS
DOI: 10.1016/j.celrep.2012.09.033
关键词
-
类别
资金
- Fonds de Recherche en Sante du Quebec (FRSQ)
- Canadian Institutes of Health Research (CIHR)
- Terry Fox Foundation through an award from the National Cancer Institute of Canada (NCIC)
- CIHR [MOP-67070, MOP-93811]
Senescence is a cellular response preventing tumorigenesis. The Ras oncogene is frequently activated or mutated in human cancers, but Ras activation is insufficient to transform primary cells. In a search for cooperating oncogenes, we identify the lysine demethylase JMJD2A/KDM4A. We show that JMJD2A functions as a negative regulator of Ras-induced senescence and collaborates with oncogenic Ras to promote cellular transformation by negatively regulating the p53 pathway. We find CHD5, a known tumor suppressor regulating p53 activity, as a target of JMJD2A. The expression of JMJD2A inhibits Ras-mediated CHD5 induction leading to a reduced activity of the p53 pathway. In addition, we show that JMJD2A is overexpressed in mouse and human lung cancers. Depletion of JMJD2A in the human lung cancer cell line A549 bearing an activated K-Ras allele triggers senescence. We propose that JMJD2A is an oncogene that represents a target for Ras-expressing tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据