Genetic suppression of polyglutamine toxicity in Drosophila

被引：444
作者：
Kazemi-Esfarjani, P [1 ]
Benzer, S [1 ]
机构：
[1] CALTECH, Div Biol, Pasadena, CA 91125 USA
来源：
SCIENCE | 2000年 / 287卷 / 5459期
关键词：
D O I：
10.1126/science.287.5459.1837
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
A Drosophila model for Huntington's and other polyglutamine diseases was used to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye. Among 7000 P-element insertions, several suppressor strains were isolated, two of which Led to the discovery of the suppressor genes described here. The predicted product of one, dHDJ1, is homologous to human heat shock protein 40/HDJ1. That of the second, dTPR2, is homologous to the human tetratricopeptide repeat protein 2. Each of these molecules contains a chaperone-related J domain. Their suppression of polyglutamine toxicity was verified in transgenic flies.
引用
收藏
页码：1837 / 1840
页数：4
相关论文
共 31 条
[1]   The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling [J].
Bergmann, A ;
Agapite, J ;
McCall, K ;
Steller, H .
CELL, 1998, 95 (03) :331-341
[2]  
BRAND AH, 1993, DEVELOPMENT, V118, P401
[3]   Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1 [J].
Cummings, CJ ;
Mancini, MA ;
Antalffy, B ;
DeFranco, DB ;
Orr, HT ;
Zoghbi, HY .
NATURE GENETICS, 1998, 19 (02) :148-154
[4]   DNAJ-LIKE PROTEINS - MOLECULAR CHAPERONES AND SPECIFIC REGULATORS OF HSP70 [J].
CYR, DM ;
LANGER, T ;
DOUGLAS, MG .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (04) :176-181
[5]   THE PROSPERO GENE SPECIFIES CELL FATES IN THE DROSOPHILA CENTRAL-NERVOUS-SYSTEM [J].
DOE, CQ ;
CHULAGRAFF, Q ;
WRIGHT, DM ;
SCOTT, MP .
CELL, 1991, 65 (03) :451-464
[6]  
ELLIS MC, 1993, DEVELOPMENT, V119, P855
[7]   Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye [J].
Freeman, M .
CELL, 1996, 87 (04) :651-660
[8]   Topological characteristics of helical repeat proteins [J].
Groves, MR ;
Barford, D .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1999, 9 (03) :383-389
[9]   Genomic cloning of a human heat shock protein 40 (Hsp40) gene (HSPF1) and its chromosomal localization to 19p13.2 [J].
Hata, M ;
Okumura, K ;
Seto, M ;
Ohtsuka, K .
GENOMICS, 1996, 38 (03) :446-449
[10]   Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons [J].
Jackson, GR ;
Salecker, I ;
Dong, XZ ;
Yao, X ;
Arnheim, N ;
Faber, PW ;
MacDonald, ME ;
Zipursky, SL .
NEURON, 1998, 21 (03) :633-642
1234