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PMID: 20688984 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.

Science (New York, N.Y.) ·Vol. 329 ·No. 5996 ·2010-09-03 ·Pages 1215-8

Cui J, Yao Q, Li S, Ding X, Lu Q, Mao H, Liu L, Zheng N, Chen S, Shao F

Abstract

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 Gln40 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.

MeSH Terms
Amidohydrolases/metabolism Bacterial Proteins/metabolism Burkholderia/pathogenicity Burkholderia pseudomallei/metabolism,pathogenicity Cell Cycle Cell Line Cullin Proteins/metabolism Enteropathogenic Escherichia coli/metabolism,pathogenicity Escherichia coli Proteins/genetics,metabolism Glutamine/metabolism HeLa Cells Humans NEDD8 Protein Point Mutation Stress Fibers/metabolism Transfection Ubiquitin/metabolism Ubiquitin C/metabolism Ubiquitin-Conjugating Enzymes/metabolism Ubiquitin-Protein Ligases/metabolism Ubiquitination Ubiquitins/metabolism
Chemicals
Bacterial Proteins Cif protein, E coli Cullin Proteins Escherichia coli Proteins NEDD8 Protein NEDD8 protein, human Ubiquitin Ubiquitin C Ubiquitins Glutamine Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Amidohydrolases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Cui Jixin
Graduate Program in Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing 100730, China.
Yao Qing
Li Shan
Ding Xiaojun
Lu Qiuhe
Mao Haibin
Liu Liping
Zheng Ning
Chen She
Shao Feng
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1193844
Published
2010-09-03
Epub
2010-00-05
Pages
1215-8
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3031172
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIAAA NIH HHS · R01 AA022309 · United States
NCI NIH HHS · R01 CA107134 · United States
NCI NIH HHS · R01 CA107134-08 · United States
External Links
PubMed source DOI: 10.1126/science.1193844 PMC Full Text View journal details
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