Document Detail


A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling.
MedLine Citation:
PMID:  17719540     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The gut epithelium self-renews every several days, providing an important innate defense system that limits bacterial colonization. Nevertheless, many bacterial pathogens, including Shigella, efficiently colonize the intestinal epithelium. Here, we show that the Shigella effector IpaB, when delivered into epithelial cells, causes cell-cycle arrest by targeting Mad2L2, an anaphase-promoting complex/cyclosome (APC) inhibitor. Cyclin B1 ubiquitination assays revealed that APC undergoes unscheduled activation due to IpaB interaction with the APC inhibitor Mad2L2. Synchronized HeLa cells infected with Shigella failed to accumulate Cyclin B1, Cdc20, and Plk1, causing cell-cycle arrest at the G2/M phase in an IpaB/Mad2L2-dependent manner. IpaB/Mad2L2-dependent cell-cycle arrest by Shigella infection was also demonstrated in rabbit intestinal crypt progenitors, and the IpaB-mediated arrest contributed to efficient colonization of the host cells. These results strongly indicate that Shigella employ special tactics to influence epithelial renewal in order to promote bacterial colonization of intestinal epithelium.
Authors:
Hiroki Iwai; Minsoo Kim; Yuko Yoshikawa; Hiroshi Ashida; Michinaga Ogawa; Yukihiro Fujita; Daniel Muller; Teruo Kirikae; Peter K Jackson; Shuji Kotani; Chihiro Sasakawa
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  130     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-27     Completed Date:  2007-10-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  611-23     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / metabolism*
Cell Cycle / physiology*
Cell Cycle Proteins / physiology
Cell Division
Dysentery, Bacillary / pathology
G2 Phase
Glutathione Transferase / metabolism
Green Fluorescent Proteins / metabolism
Hela Cells
Humans
Ileum / microbiology
Immunohistochemistry
Intestinal Mucosa / microbiology
Models, Biological
Precipitin Tests
Proliferating Cell Nuclear Antigen / metabolism
Proteins / genetics,  metabolism*
RNA Interference
Rabbits
Recombinant Proteins / metabolism
Shigella / metabolism*,  pathogenicity
Two-Hybrid System Techniques
Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors*
Ubiquitins / analysis
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Cell Cycle Proteins; 0/MAD2L2 protein, human; 0/Proliferating Cell Nuclear Antigen; 0/Proteins; 0/Recombinant Proteins; 0/Ubiquitins; 127384-62-7/ipaB protein, Shigella; 147336-22-9/Green Fluorescent Proteins; EC 2.5.1.18/Glutathione Transferase; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting complex

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