Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 329 (5996): 1215-1218

Copyright © 2010 by the American Association for the Advancement of Science

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

Jixin Cui,1,2 Qing Yao,2 Shan Li,2 Xiaojun Ding,2 Qiuhe Lu,2 Haibin Mao,3 Liping Liu,2 Ning Zheng,3,4 She Chen,2 Feng Shao2,*

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.

1 Graduate Program in Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing 100730, China.
2 National Institute of Biological Sciences, Beijing, 102206, China.
3 Department of Pharmacology, Box 357280, University of Washington, Seattle, WA, 98195, USA.
4 Department of Pharmacology and Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, WA, 98195, USA.

* To whom correspondence should be addressed. E-mail: shaofeng{at}nibs.ac.cn


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
What a Difference a Dalton Makes: Bacterial Virulence Factors Modulate Eukaryotic Host Cell Signaling Systems via Deamidation.
E. J. Washington, M. J. Banfield, and J. L. Dangl (2013)
Microbiol. Mol. Biol. Rev. 77, 527-539
   Abstract »    Full Text »    PDF »
The Cyclomodulin Cycle Inhibiting Factor (CIF) Alters Cullin Neddylation Dynamics.
T. B. Toro, J. I. Toth, and M. D. Petroski (2013)
J. Biol. Chem. 288, 14716-14726
   Abstract »    Full Text »    PDF »
Bacterial Subversion of Host Innate Immune Pathways.
L. A. Baxt, A. C. Garza-Mayers, and M. B. Goldberg (2013)
Science 340, 697-701
   Abstract »    Full Text »    PDF »
General Aspects and Recent Advances on Bacterial Protein Toxins.
E. Lemichez and J. T. Barbieri (2013)
Cold Spring Harb Perspect Med 3, a013573
   Abstract »    Full Text »    PDF »
Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.
Q. Yao, J. Cui, J. Wang, T. Li, X. Wan, T. Luo, Y.-N. Gong, Y. Xu, N. Huang, and F. Shao (2012)
PNAS 109, 20395-20400
   Abstract »    Full Text »    PDF »
Subversion of Cell Signaling by Pathogens.
N. M. Alto and K. Orth (2012)
Cold Spring Harb Perspect Biol 4, a006114
   Abstract »    Full Text »    PDF »
The molecular basis of ubiquitin-like protein NEDD8 deamidation by the bacterial effector protein Cif.
A. Crow, R. K. Hughes, F. Taieb, E. Oswald, and M. J. Banfield (2012)
PNAS 109, E1830-E1838
   Abstract »    Full Text »    PDF »
A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A.
A. Cruz-Migoni, G. M. Hautbergue, P. J. Artymiuk, P. J. Baker, M. Bokori-Brown, C.-T. Chang, M. J. Dickman, A. Essex-Lopresti, S. V. Harding, N. M. Mahadi, et al. (2011)
Science 334, 821-824
   Abstract »    Full Text »    PDF »
Listeria Unwinds Host DNA.
J. R. Rohde (2011)
Science 331, 1271-1272
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882