E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis

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Title
E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis
Author(s)
Cho Rok Jung; K S Hwang; J Yoo; Won Kyung Cho; J M Kim; W H Kim; Dong Soo Im
Bibliographic Citation
Nature Medicine, vol. 12, no. 7, pp. 809-816
Publication Year
2006
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.
ISSN
1078-8956
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/nm1440
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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