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Updated: May 11, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
TRAF6 upregulates expression of HIF-1α and promotes tumor angiogenesis
Heng Sun1, Xue-Bing Li, Ya Meng
1The Key Lab of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Abstract:
TNF receptor (TNFR)-associated factor TRAF6 is a key activator of NF-κB, 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)-1α. TRAF6 affects HIF-1α protein levels but has little effect on mRNA level. TRAF6 increases HIF-1α protein independent of oxygen. We found that TRAF6 binds HIF-1α and mediates its K63-linked polyubiquitination. The E3 ligase activity of TRAF6 was required to increase HIF-1α protein levels. Finally, we showed that TRAF6 promoted tumor angiogenesis and growth. Our results reveal how TRAF6 functions to upregulate HIF-1α expression and promote tumor angiogenesis.
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