Document Detail

Cell cycle arrest induced by the bacterial adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis.
MedLine Citation:
PMID:  20946259     Owner:  NLM     Status:  MEDLINE    
Bacillus anthracis oedema toxin (ET) and Bordetella pertussis adenylate cyclase toxin (ACT) enter host cells and produce cAMP. To understand the cellular consequences, we exposed J774 cells to these toxins at ng ml(-1) (pM) concentrations, then followed cell number and changes in cell signalling pathways. Under these conditions, both toxins produce a concentration-dependent inhibition of cell proliferation without cytotoxicity. ET and ACT increase the proportion of cells in G(1) /G(0) and reduce S phase, such that a single addition of ET or ACT inhibits cell division for 3-6 days. Treatment with ET or ACT produces striking changes in proteins controlling cell cycle, including virtual elimination of phosphorylated ERK 1/2 and Cyclin D1 and increases in phospho-CREB and p27(Kip1) . Importantly, PD98059, a MEK inhibitor, elicits a comparable reduction in Cyclin D1 to that produced by the toxins and blocks proliferation. These data show that non-lethal concentrations of ET and ACT impose a prolonged block on the proliferation of J774 cells by impairment of the progression from G(1) /G(0) to S phase in a process involving cAMP-mediated increases in phospho-CREB and p27(Kip1) and reductions in phospho-ERK 1/2 and Cyclin D1. This phenomenon represents a new mechanism by which these toxins affect host cells.
Mary C Gray; Erik L Hewlett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-14
Journal Detail:
Title:  Cellular microbiology     Volume:  13     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-20     Completed Date:  2011-03-31     Revised Date:  2014-08-21    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  123-34     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
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MeSH Terms
Adenylate Cyclase Toxin / toxicity*
Antigens, Bacterial / toxicity*
Bacillus anthracis / pathogenicity*
Bacterial Toxins / toxicity*
Bordetella pertussis / pathogenicity*
Cell Cycle / drug effects*
Cell Line
Cell Proliferation / drug effects
Cell Survival
Cyclic AMP Response Element-Binding Protein / biosynthesis
Cyclin D1 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
Gene Expression Profiling
Macrophages / drug effects
Mitogen-Activated Protein Kinase 1 / biosynthesis
Mitogen-Activated Protein Kinase 3 / biosynthesis
Grant Support
Reg. No./Substance:
0/Adenylate Cyclase Toxin; 0/Antigens, Bacterial; 0/Bacterial Toxins; 0/Ccnd1 protein, mouse; 0/Cdkn1b protein, mouse; 0/Creb1 protein, mouse; 0/Cyclic AMP Response Element-Binding Protein; 0/anthrax toxin; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC Protein Kinase 1; EC Protein Kinase 3

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