Abstract
Germ-line mutations of the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of human tumors, and somatic mutations of this gene have been identified in sporadic renal cell carcinomas and cerebellar hemangioblastomas. Two transcriptional elongation factors, Elongin B and C, were shown to bind in vitro and in vivo to a short, colinear region of the VHL protein (pVHL) that is frequently mutated in human tumors. A peptide replica of this region inhibited binding of pVHL to Elongin B and C whereas a point-mutant derivative, corresponding to a naturally occurring VHL missense mutation, had no effect. These results suggest that the tumor suppression function of pVHL may be linked to its ability to bind to Elongin B and C.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Carcinoma, Renal Cell
-
Elongin
-
Genes, Tumor Suppressor*
-
Germ-Line Mutation
-
Humans
-
Ligases*
-
Mice
-
Molecular Sequence Data
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism*
-
Point Mutation
-
Recombinant Fusion Proteins / metabolism
-
Transcription Factors / metabolism*
-
Transfection
-
Tumor Cells, Cultured
-
Tumor Suppressor Proteins*
-
Ubiquitin-Protein Ligases*
-
Von Hippel-Lindau Tumor Suppressor Protein
-
von Hippel-Lindau Disease / genetics
Substances
-
ELOB protein, human
-
Elob protein, mouse
-
Elongin
-
Nuclear Proteins
-
Recombinant Fusion Proteins
-
Transcription Factors
-
Tumor Suppressor Proteins
-
Ubiquitin-Protein Ligases
-
Von Hippel-Lindau Tumor Suppressor Protein
-
Ligases
-
VHL protein, human