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

Kim M. Lonergan, Othon Iliopoulos, Michael Ohh, Takumi Kamura, Ronald C. Conaway, Joan Weliky Conaway, William G. Kaelin

Research output: Contribution to journalArticlepeer-review

323 Scopus citations

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 hypoxiainducible 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.

Original languageEnglish (US)
Pages (from-to)732-741
Number of pages10
JournalMolecular and cellular biology
Volume18
Issue number2
DOIs
StatePublished - Feb 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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