Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2

Mol Cell Biol. 1998 Feb;18(2):732-41. doi: 10.1128/MCB.18.2.732.

Abstract

The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Hypoxia
  • Cullin Proteins*
  • Elongin
  • Genes, Tumor Suppressor*
  • Humans
  • Ligases*
  • Macromolecular Substances
  • Molecular Sequence Data
  • Proteins / metabolism*
  • RNA, Messenger / biosynthesis*
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein

Substances

  • CUL2 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cullin Proteins
  • ELOC protein, human
  • Elongin
  • Macromolecular Substances
  • Proteins
  • RNA, Messenger
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human