Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.
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.
Cui
Jixin
J
Graduate Program in Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing 100730, China.
Yao
Qing
Q
Li
Shan
S
Ding
Xiaojun
X
Lu
Qiuhe
Q
Mao
Haibin
H
Liu
Liping
L
Zheng
Ning
N
Chen
She
S
Shao
Feng
F
D000581:Amidohydrolases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D019117:Burkholderia / Q000472:pathogenicity; D016957:Burkholderia pseudomallei / Q000378:metabolism* / Q000472:pathogenicity; D002453:Cell Cycle; D002460:Cell Line; D044842:Cullin Proteins / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D000075687:NEDD8 Protein; D017354:Point Mutation; D022502:Stress Fibers / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D025822:Ubiquitin C / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism*
D001426:Bacterial Proteins; C481998:Cif protein, E coli; D044842:Cullin Proteins; D029968:Escherichia coli Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D025801:Ubiquitin; D025822:Ubiquitin C; D014452:Ubiquitins; D005973:Glutamine; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000581:Amidohydrolases