Glutamine Deamidation and Dysfunction of Ubiquitin/NEDD8 Induced by a Bacterial Effector Family

被引：161

作者：

Cui, Jixin ^{[1
,2
,3
]}

Yao, Qing ^{[1
]}

Li, Shan ^{[1
]}

Ding, Xiaojun ^{[1
]}

Lu, Qiuhe ^{[1
]}

Mao, Haibin ^{[4
]}

Liu, Liping ^{[1
]}

Zheng, Ning ^{[4
,5
,6
]}

Chen, She ^{[1
]}

Shao, Feng ^{[1
]}

机构：

[1] Natl Inst Biol Sci, Beijing 102206, Peoples R China

[2] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China

[3] Beijing Union Med Coll, Beijing 100730, Peoples R China

[4] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA

[5] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA

[6] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

来源：

SCIENCE | 2010年 / 329卷 / 5996期

基金：

美国国家卫生研究院;

关键词：

HOST-CELL CYCLE; ESCHERICHIA-COLI; CYCLOMODULIN CIF; PROTEIN; LIGASE; DEGRADATION; CONJUGATION; ACTIVATION; INSIGHTS; BLOCKS;

D O I：

10.1126/science.1193844

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 family of bacterial effectors including Cif homolog from Burkholderia pseudomallei (CHBP) and Cif from Enteropathogenic Escherichia coli (EPEC) adopt a functionally important papain-like hydrolytic fold. We show here that CHBP was a potent inhibitor of the eukaryotic ubiquitination pathway. CHBP acted as a deamidase that specifically and efficiently deamidated Gln(40) in ubiquitin and ubiquitin-like protein NEDD8 both in vitro and during Burkholderia infection. Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif selectively deamidated NEDD8, which abolished the activity of neddylated Cullin-RING ubiquitin ligases (CRLs). Ubiquitination and ubiquitin-dependent degradation of multiple CRL substrates were impaired by Cif in EPEC-infected cells. Mutations of substrate-contacting residues in Cif abolished or attenuated EPEC-induced cytopathic phenotypes of cell cycle arrest and actin stress fiber formation.

引用

页码：1215 / 1218

页数：4

共 21 条

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