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

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.
AuthorsJixin Cui, Qing Yao, Shan Li, Xiaojun Ding, Qiuhe Lu, Haibin Mao, Liping Liu, Ning Zheng, She Chen, Feng Shao
JournalScience (New York, N.Y.) (Science) Vol. 329 Issue 5996 Pg. 1215-8 (Sep 03 2010) ISSN: 1095-9203 [Electronic] United States
PMID20688984 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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
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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