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; Othon Iliopoulos; Michael Ohh; Takumi Kamura; Ronald C. Conaway; Joan Weliky Conaway; William G. Kaelin

doi:10.1128/MCB.18.2.732

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, Othon Iliopoulos, Michael Ohh, Takumi Kamura, Ronald C. Conaway, Joan Weliky Conaway, William G. Kaelin

Research output: Contribution to journal › Article › peer-review

341 Scopus citations

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 hypoxiainducible 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.

Original language	English (US)
Pages (from-to)	732-741
Number of pages	10
Journal	Molecular and cellular biology
Volume	18
Issue number	2
DOIs	https://doi.org/10.1128/MCB.18.2.732
State	Published - Feb 1998
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1128/MCB.18.2.732

Cite this

@article{d536d8dc663b4710838ed749ef2bb68d,

title = "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 hypoxiainducible 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.",

author = "Lonergan, {Kim M.} and Othon Iliopoulos and Michael Ohh and Takumi Kamura and Conaway, {Ronald C.} and Conaway, {Joan Weliky} and Kaelin, {William G.}",

year = "1998",

month = feb,

doi = "10.1128/MCB.18.2.732",

language = "English (US)",

volume = "18",

pages = "732--741",

journal = "Molecular and cellular biology",

issn = "0270-7306",

publisher = "Taylor and Francis Ltd.",

number = "2",

}

TY - JOUR

T1 - Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2

AU - Lonergan, Kim M.

AU - Iliopoulos, Othon

AU - Ohh, Michael

AU - Kamura, Takumi

AU - Conaway, Ronald C.

AU - Conaway, Joan Weliky

AU - Kaelin, William G.

PY - 1998/2

Y1 - 1998/2

N2 - 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 hypoxiainducible 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.

AB - 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 hypoxiainducible 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.

UR - http://www.scopus.com/inward/record.url?scp=0031907152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031907152&partnerID=8YFLogxK

U2 - 10.1128/MCB.18.2.732

DO - 10.1128/MCB.18.2.732

M3 - Article

C2 - 9447969

AN - SCOPUS:0031907152

SN - 0270-7306

VL - 18

SP - 732

EP - 741

JO - Molecular and cellular biology

JF - Molecular and cellular biology

IS - 2

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this