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PMID: 10421634 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity.

Genes & development ·Vol. 13 ·No. 14 ·1999-07-15 ·Pages 1822-33

Lisztwan J, Imbert G, Wirbelauer C, Gstaiger M, Krek W

Abstract

pVHL, the product of the VHL tumor suppressor gene, plays an important role in the regulation of cell growth and differentiation of human kidney cells, and inactivation of the VHL gene is the most frequent genetic event in human kidney cancer. The biochemical function of pVHL is unknown. Here we report that pVHL exists in vivo in a complex that displays ubiquitination-promoting activity in conjunction with the universally required components E1, E2, and ubiquitin. pVHL-associated ubiquitination activity requires, at a minimum, pVHL to bind elongin C and Cul-2, relatives of core components of SCF (Skp1-Cdc53/Cul-1-F-box protein) E3 ligase complexes. Notably, certain tumor-derived mutants of pVHL demonstrate loss of associated ubiquitination promoting activity. These results identify pVHL as a component of a potential SCF-like E3 ubiquitin-protein ligase complex and suggest a direct link between pVHL tumor suppressor and the process of ubiquitination.

MeSH Terms
Amino Acid Sequence Base Sequence Cell Extracts DNA Primers Genes, Tumor Suppressor Humans Kidney Neoplasms/metabolism Ligases/genetics,metabolism Molecular Sequence Data Mutation Precipitin Tests Proteins/genetics,metabolism Recombinant Proteins/genetics,metabolism Sequence Homology, Amino Acid Tumor Cells, Cultured Tumor Suppressor Proteins Ubiquitin-Protein Ligases Ubiquitins/metabolism Von Hippel-Lindau Tumor Suppressor Protein
Chemicals
Cell Extracts DNA Primers Proteins Recombinant Proteins Tumor Suppressor Proteins Ubiquitins Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein Ligases VHL protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lisztwan J
Friedrich Miescher Institut, CH-4058 Basel, Switzerland.
Imbert G
Wirbelauer C
Gstaiger M
Krek W
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.14.1822
Published
1999-07-15
Pages
1822-33
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316884
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.13.14.1822 PMC Full Text View journal details
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