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

被引：316

作者：

Lonergan, KM

Iliopoulos, O

Ohh, M

Kamura, T

Conaway, RC

Conaway, JW

Kaelin, WG

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA

[3] Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA

[4] Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA

[5] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 1998年 / 18卷 / 02期

关键词：

D O I：

10.1128/MCB.18.2.732

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：732 / 741

页数：10

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