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

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.
Authors	K M Lonergan, O Iliopoulos, M Ohh, T Kamura, R C Conaway, J W Conaway, W G Kaelin Jr
Journal	Molecular and cellular biology (Mol Cell Biol) Vol. 18 Issue 2 Pg. 732-41 (Feb 1998) ISSN: 0270-7306 [Print] United States
PMID	9447969 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	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
Topics	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

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