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.
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Authors | Jixin Cui, Qing Yao, Shan Li, Xiaojun Ding, Qiuhe Lu, Haibin Mao, Liping Liu, Ning Zheng, She Chen, Feng Shao |
Journal | Science (New York, N.Y.)
(Science)
Vol. 329
Issue 5996
Pg. 1215-8
(Sep 03 2010)
ISSN: 1095-9203 [Electronic] United States |
PMID | 20688984
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- 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
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Topics |
- 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)
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