Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2-Reference-Cited by-同舟云学术

Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2

Published:1998-02 Issue:2 Volume:18 Page:732-741
ISSN:0270-7306
Container-title:Molecular and Cellular Biology
language:en
Short-container-title:Mol Cell Biol

Author:

Lonergan Kim M.¹²,Iliopoulos Othon¹²,Ohh Michael¹²,Kamura Takumi³,Conaway Ronald C.³,Conaway Joan Weliky³⁴⁵,Kaelin William G.¹²

Affiliation:

1. Dana-Farber Cancer Institute 1 and

2. Brigham and Women’s Hospital, Harvard Medical School, 2 Boston, Massachusetts 02115;

3. Program in Molecular and Cell Biology 3 and

4. Howard Hughes Medical Institute, 4 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; and

5. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731905

Abstract

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% O 2 ) 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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Link

https://journals.asm.org/doi/pdf/10.1128/MCB.18.2.732

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