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PMID: 9447969 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 ·Vol. 18 ·No. 2 ·1998-02-00 ·Pages 732-41

Lonergan KM, Iliopoulos O, Ohh M, Kamura T, Conaway RC, Conaway JW, Kaelin WG

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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lonergan K M
Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Iliopoulos O
Ohh M
Kamura T
Conaway R C
Conaway J W
Kaelin W G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.2.732
Published
1998-02-00
Pages
732-41
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC108784
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.18.2.732 PMC Full Text View journal details
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