期刊
CANCER RESEARCH
卷 73, 期 15, 页码 4950-4959出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-0370
关键词
-
类别
资金
- Natural Science Foundation of China [30970586, 31270829]
- Chinese Academy of Sciences [KSCX2-EW-R-09]
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [2012CSP003]
TNF receptor (TNFR)-associated factor TRAF6 is a key activator of NF-kappa B, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upregulates expression of hypoxia-inducible factor (HIF)-1 alpha. TRAF6 affects HIF-1 alpha protein levels but has little effect on mRNA level. TRAF6 increases HIF-1 alpha protein independent of oxygen. We found that TRAF6 binds HIF-1 alpha and mediates its K63-linked polyubiquitination. The E3 ligase activity of TRAF6 was required to increase HIF-1 alpha protein levels. Finally, we showed that TRAF6 promoted tumor angiogenesis and growth. Our results reveal how TRAF6 functions to upregulate HIF-1 alpha expression and promote tumor angiogenesis. Cancer Res; 73(15); 4950-9. (C) 2013 AACR.
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