pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation

Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11661-6. doi: 10.1073/pnas.95.20.11661.

Abstract

The von Hippel-Lindau (VHL) gene encodes a protein consisting of 213 amino acid residues with an apparent molecular mass of 30 kDa (pVHL30). Here we show that cells also produce a VHL protein (pVHL19) that appears to arise as a result of internal translation from the second methionine within the VHL ORF. pVHL30 resides primarily in the cytosol, with less amounts found in the nucleus or associated with cell membranes. In contrast pVHL19, in biochemical fractionation experiments, is equally distributed between the nucleus and cytosol and is not found in association with membranes. pVHL19, like pVHL30, can bind to elongin B, elongin C, and Hs-Cul2 in coimmunoprecipitation assays and can inhibit the production of hypoxia-inducible proteins such as vascular endothelial growth factor (VEGF) and GLUT1 when reintroduced into renal carcinoma cells that lack a wild-type VHL allele. Thus, cells contain two biologically active VHL gene products.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • DNA Primers / genetics
  • Endothelial Growth Factors / metabolism
  • Genes, Tumor Suppressor*
  • Glucose Transporter Type 1
  • Humans
  • Kinetics
  • Ligases*
  • Lymphokines / metabolism
  • Molecular Weight
  • Monosaccharide Transport Proteins / metabolism
  • Mutation
  • Peptide Chain Initiation, Translational
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Von Hippel-Lindau Tumor Suppressor Protein
  • von Hippel-Lindau Disease / genetics*

Substances

  • DNA Primers
  • Endothelial Growth Factors
  • Glucose Transporter Type 1
  • Lymphokines
  • Monosaccharide Transport Proteins
  • Proteins
  • Recombinant Proteins
  • SLC2A1 protein, human
  • Tumor Suppressor Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human