| The bacterial effector Cif interferes with SCF ubiquitin ligase function by inhibiting deneddylation of Cullin1. | |
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MedLine Citation:
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PMID: 20850415 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cycle inhibiting factor (Cif) is one of the effectors delivered into epithelial cells by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) via the type III secretion system (TTSS). Cif family proteins, which inhibit host cell-cycle progression via mechanisms not yet precisely understood, are highly conserved among EPEC, EHEC, Yersinia pseudotuberculosis, Photorhabdus luminescens and Burkholderia pseudomallei. Levels of several proteins relevant to cell-cycle progression are modulated by Cullin-RING ligases (CRLs), which in turn are activated by conjugation and deconjugation of NEDD8 to Cullins. Here we show that Cif interacts with NEDD8 and interferes with SCF (Skp1-Cullin1-F-box protein) complex ubiquitin ligase function. We found that neddylated Cullin family proteins accumulated and ubiquitination of p27 decreased in cells infected with EPEC. Consequently, Cif stabilized SCF substrates such as CyclinD1, Cdt1, and p27, and caused G1 cell-cycle arrest. Using time-lapse-imaging of fluorescent ubiquitination-based cell-cycle indicator (Fucci)-expressing cells, we were able to monitor cell-cycle progression during EPEC infection and confirmed the arrest of infected cells at G1. Our in vitro and in vivo data show that Cif-NEDD8 interaction inhibits deneddylation of Cullins, suppresses CRL activity and induces G1 arrest. We thus conclude that the bacterial effector Cif interferes with neddylation-mediated cell-cycle control. |
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Authors:
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Hanako Morikawa; Minsoo Kim; Hitomi Mimuro; Claire Punginelli; Tomohiro Koyama; Shinya Nagai; Atsushi Miyawaki; Kazuhiro Iwai; Chihiro Sasakawa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-17 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 401 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 268-74 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Cullin Proteins / metabolism* Enteropathogenic Escherichia coli / metabolism* Escherichia coli Infections / metabolism* Escherichia coli Proteins / metabolism* G1 Phase Hela Cells Humans SKP Cullin F-Box Protein Ligases / antagonists & inhibitors* Ubiquitins / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cif protein, E coli; 0/Cullin 1; 0/Cullin Proteins; 0/Escherichia coli Proteins; 0/NEDD8 protein, human; 0/Ubiquitins; EC 6.3.2.19/SKP Cullin F-Box Protein Ligases |
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