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
收藏
页码：732 / 741
页数：10
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