Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2.
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.
Mesh Terms:
Amino Acid Sequence, Carrier Proteins, Cell Cycle Proteins, Cell Hypoxia, Cullin Proteins, Genes, Tumor Suppressor, Humans, Ligases, Macromolecular Substances, Molecular Sequence Data, Proteins, RNA, Messenger, Transcription Factors, Tumor Cells, Cultured, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Von Hippel-Lindau Tumor Suppressor Protein
Amino Acid Sequence, Carrier Proteins, Cell Cycle Proteins, Cell Hypoxia, Cullin Proteins, Genes, Tumor Suppressor, Humans, Ligases, Macromolecular Substances, Molecular Sequence Data, Proteins, RNA, Messenger, Transcription Factors, Tumor Cells, Cultured, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Von Hippel-Lindau Tumor Suppressor Protein
Mol. Cell. Biol.
Date: Feb. 01, 1998
PubMed ID: 9447969
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