Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity

被引：23

作者：

Aso, T

Yamazaki, K

Aigaki, T

Kitajima, S

机构：

[1] Japanese Fdn Canc Res, Inst Canc, Dept Viral Oncol, Toshima Ku, Tokyo 1708455, Japan

[2] Tokyo Med & Dent Univ, Med Res Inst, Dept Biochem Genet, Bunkyo Ku, Tokyo 1138510, Japan

[3] Tokyo Metropolitan Univ, Dept Biol Sci, Tokyo 1920397, Japan

[4] Japan Sci & Technol Corp, PRESTO, Tokyo 1920397, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2000年 / 276卷 / 01期

关键词：

VHL; Elongin; cullin; ubiquitin ligase; E3; hypoxia-inducible factor;

D O I：

10.1006/bbrc.2000.3451

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：

Mutations of the von Hippel-Lindau (VHL) tumor suppressor gene predispose individuals to a variety of human tumors, including renal cell carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma, Here we report on the identification and characterization of the Drosophila homolog of VHL, The predicted amino acid sequence of Drosophila VHL protein shows 29% identity and 44% similarity to that of human VHL protein. Biochemical studies have shown that Drosophila VHL protein binds to Elongins B and C directly, and via this Elongin BC complex, associates with Cul-2 and Rbx1. Like human VHL, Drosophila MIL complex containing Cul-2, Rbx1, Elongins B and C, exhibits E3 ubiquitin ligase activity. In addition, we provide evidence that hypoxia-inducible factor (HIF)-1 alpha is the ubiquitination target of both human and Drosophila VHL complexes. (C) 2000 Academic Press.

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收藏

页码：355 / 361

页数：7

相关论文

共 22 条

[1] 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

[2] ELONGIN (SIII) - A MULTISUBUNIT REGULATOR OF ELONGATION BY RNA-POLYMERASE-II [J].

ASO, T ;

LANE, WS ;

CONAWAY, JW ;

CONAWAY, RC .

SCIENCE, 1995, 269 (5229) :1439-1443

[3] Identification and characterization of Elongin A2, a new member of the Elongin family of transcription elongation factors, specifically expressed in the testis [J].

Aso, T ;

Yamazaki, K ;

Amimoto, K ;

Kuroiwa, A ;

Higashi, H ;

Matsuda, Y ;

Kitajima, S ;

Hatakeyama, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (09) :6546-6552

[4] Control of cell lineage-specific development and transcription by bHLH-PAS proteins [J].

Crews, ST .

GENES & DEVELOPMENT, 1998, 12 (05) :607-620

[5] 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

[6] Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene [J].

Gnarra, JR ;

Zhou, SB ;

Merrill, MJ ;

Wagner, JR ;

Krumm, A ;

Papavassiliou, E ;

Oldfield, EH ;

Klausner, RD ;

Linehan, WM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (20) :10589-10594

[7] Negative regulation of hypoxia-inducible genes by the von Hippel Lindau protein [J].

Iliopoulos, O ;

Levy, AP ;

Jiang, C ;

Kaelin, WG ;

Goldberg, MA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (20) :10595-10599

[8] Identification of the von Hippel-Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex [J].

Iwai, K ;

Yamanaka, K ;

Kamura, T ;

Minato, N ;

Conaway, RC ;

Canaway, JW ;

Klausner, RD ;

Pause, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12436-12441

[9] The VHL tumour-suppressor gene paradigm [J].

Kaelin, WG ;

Maher, ER .

TRENDS IN GENETICS, 1998, 14 (10) :423-426

[10] Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase [J].

Kamura, T ;

Koepp, DM ;

Conrad, MN ;

Skowyra, D ;

Moreland, RJ ;

Iliopoulos, O ;

Lane, WS ;

Kaelin, WG ;

Elledge, SJ ;

Conaway, RC ;

Harper, JW ;

Conway, JW .

SCIENCE, 1999, 284 (5414) :657-661