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Escherichia coli cytolethal distending toxin blocks the HeLa cell cycle at the G2/M transition by preventing cdc2 protein kinase dephosphorylation and activation

Comayras, Chrystel and Tasca, Christian and Pérès, Sylvie Yvonne and Ducommun, Bernard and Oswald, Eric and Rycke, Jean de Escherichia coli cytolethal distending toxin blocks the HeLa cell cycle at the G2/M transition by preventing cdc2 protein kinase dephosphorylation and activation. (1997) Infection and immunity, vol. 6 (n° 12). pp. 5088-5095. ISSN 0019-9567

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Official URL: http://iai.asm.org/cgi/reprint/65/12/5088

Abstract

Cytolethal distending toxins (CDT) constitute an emerging heterogeneous family of bacterial toxins whose common biological property is to inhibit the proliferation of cells in culture by blocking their cycle at G2/M phase. In this study, we investigated the molecular mechanisms underlying the block caused by CDT from Escherichia coli on synchronized HeLa cell cultures. To this end, we studied specifically the behavior of the two subunits of the complex that determines entry into mitosis, i.e., cyclin B1, the regulatory unit, and cdc2 protein kinase, the catalytic unit. We thus demonstrate that CDT causes cell accumulation in G2 and not in M, that it does not slow the progression of cells through S phase, and that it does not affect the normal increase of cyclin B1 from late S to G2. On the other hand, we show that CDT inhibits the kinase activity of cdc2 by preventing its dephosphorylation, an event which, in normal cells, triggers mitosis. This inhibitory activity was demonstrated for the three partially related CDTs so far described for E. coli. Moreover, we provide evidence that cells exposed to CDT during G2 and M phases are blocked only at the subsequent G2 phase. This observation means that the toxin triggers a mechanism of cell arrest that is initiated in S phase and therefore possibly related to the DNA damage checkpoint system.

Item Type:Article
Additional Information:Thanks to American Society for Microbiology. The original PDF of the article can be found at Infection and immunity website : http://iai.asm.org
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Institut National de la Recherche Agronomique - INRA
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT
French research institutions > Centre National de la Recherche Scientifique - CNRS
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Deposited By: Mathieu Andro

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