408회 E2-EPF UCP targets VHL suppressor and associates with tumor growt…

408회

연사 : 임 동 수, 과기부 21세기 프론티어 인간유전체기능연구사업단 단장/한국생명공학연구원 책임연구원

제목 : E2-EPF UCP targets VHL tumor suppressor and associates with tumor growth and metastasis

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-1a (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.