Author: ["Cho-Rok Jung","Kyung-Sun Hwang","Jinsang Yoo","Won-Kyung Cho","Jin-Man Kim","Woo Ho Kim","Dong-Soo Im"]
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Abstract
The von Hippel-Lindau tumor suppressor, pVHL, forms part of an E3 ubiquitin ligase complex that targets specific substrates for degradation, including hypoxia-inducible factor-1α (HIF-1α), which is involved in tumor progression and angiogenesis. It remains unclear, however, how pVHL is destabilized. Here we show that E2-EPF ubiquitin carrier protein (UCP) associates with and targets pVHL for ubiquitin-mediated proteolysis in cells, thereby stabilizing HIF-1α. UCP is detected coincidently with HIF-1α in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells. UCP level correlates inversely with pVHL level in most tumor cell lines. In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway. Our results suggest that UCP helps stabilize HIF-1α and may be a new molecular target for therapeutic intervention in human cancers.Cite this article
Jung, CR., Hwang, KS., Yoo, J. et al. E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Nat Med 12, 809–816 (2006). https://doi.org/10.1038/nm1440 