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.
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页码：732 / 741
页数：10
相关论文
共 52 条
[1]  
[Anonymous], 1992, MENDELIAN INHERITANC
[2]  
[Anonymous], 1988, Antibodies: A Laboratory Manual
[3]   The inducible elongin A elongation activation domain: Structure, function and interaction with the elongin BC complex [J].
Aso, T ;
Haque, D ;
Barstead, RJ ;
Conaway, RC ;
Conaway, JW .
EMBO JOURNAL, 1996, 15 (20) :5557-5566
[4]   SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box [J].
Bai, C ;
Sen, P ;
Hofmann, K ;
Ma, L ;
Goebl, M ;
Harper, JW ;
Elledge, SJ .
CELL, 1996, 86 (02) :263-274
[5]   VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) GENE IS EXPRESSED DIFFERENTIALLY IN NORMAL-TISSUES, MACROPHAGES, AND TUMORS [J].
BERSE, B ;
BROWN, LF ;
VANDEWATER, L ;
DVORAK, HF ;
SENGER, DR .
MOLECULAR BIOLOGY OF THE CELL, 1992, 3 (02) :211-220
[6]  
Conaway RC, 1996, METHOD ENZYMOL, V273, P194
[7]  
CONAWAY RC, UNPUB
[8]   Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues [J].
Corless, CL ;
Kibel, AS ;
Iliopoulos, O ;
Kaelin, WG .
HUMAN PATHOLOGY, 1997, 28 (04) :459-464
[9]   INHIBITION OF TRANSCRIPTION ELONGATION BY THE VHL TUMOR-SUPPRESSOR PROTEIN [J].
DUAN, DR ;
PAUSE, A ;
BURGESS, WH ;
ASO, T ;
CHEN, DYT ;
GARRETT, KP ;
CONAWAY, RC ;
CONAWAY, JW ;
LINEHAN, WM ;
KLAUSNER, RD .
SCIENCE, 1995, 269 (5229) :1402-1406
[10]   SOMATIC MUTATIONS OF THE VON HIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE IN NONFAMILIAL CLEAR-CELL RENAL-CARCINOMA [J].
FOSTER, K ;
PROWSE, A ;
VANDENBERG, A ;
FLEMING, S ;
HULSBEEK, MMF ;
CROSSEY, PA ;
RICHARDS, FM ;
CAIRNS, P ;
AFFARA, NA ;
FERGUSONSMITH, MA ;
BUYS, CHCM ;
MAHER, ER .
HUMAN MOLECULAR GENETICS, 1994, 3 (12) :2169-2173
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