Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

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

Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires... 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 1 , 2 , Othon Iliopoulos 1 , 2 , Michael Ohh 1 , 2 , Takumi Kamura 3 , Ronald C. Conaway 3 , Joan Weliky Conaway 3 , 4 , 5 and William G. Kaelin Jr. 1 , 2 , * Dana-Farber Cancer Institute 1 and Brigham and Women’s Hospital, Harvard Medical School, 2 Boston, Massachusetts 02115; Program in Molecular and Cell Biology 3 and Howard Hughes Medical Institute, 4 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190 5 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

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

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

Molecular and Cellular Biology , Volume 18 (2): 732 – Feb 1, 1998

Abstract

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 1 , 2 , Othon Iliopoulos 1 , 2 , Michael Ohh 1 , 2 , Takumi Kamura 3 , Ronald C. Conaway 3 , Joan Weliky Conaway 3 , 4 , 5 and William G. Kaelin Jr. 1 , 2 , * Dana-Farber Cancer Institute 1 and Brigham and Women’s Hospital, Harvard Medical School, 2 Boston, Massachusetts 02115; Program in Molecular and Cell Biology 3 and Howard Hughes Medical Institute, 4 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190 5 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.

Loading next page...
 
/lp/american-society-for-microbiology/regulation-of-hypoxia-inducible-mrnas-by-the-von-hippel-lindau-tumor-uhRug8HpLS

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
American Society For Microbiology
Copyright
Copyright © 1998 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
Publisher site
See Article on Publisher Site

Abstract

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 1 , 2 , Othon Iliopoulos 1 , 2 , Michael Ohh 1 , 2 , Takumi Kamura 3 , Ronald C. Conaway 3 , Joan Weliky Conaway 3 , 4 , 5 and William G. Kaelin Jr. 1 , 2 , * Dana-Farber Cancer Institute 1 and Brigham and Women’s Hospital, Harvard Medical School, 2 Boston, Massachusetts 02115; Program in Molecular and Cell Biology 3 and Howard Hughes Medical Institute, 4 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190 5 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.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Feb 1, 1998

There are no references for this article.