Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.

The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G(1) and G(2) cell cycle arrests,...

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Main Authors: Grégory Jubelin, Carolina Varela Chavez, Frédéric Taieb, Mark J Banfield, Ascel Samba-Louaka, Rika Nobe, Jean-Philippe Nougayrède, Robert Zumbihl, Alain Givaudan, Jean-Michel Escoubas, Eric Oswald
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004855&type=printable
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author Grégory Jubelin
Carolina Varela Chavez
Frédéric Taieb
Mark J Banfield
Ascel Samba-Louaka
Rika Nobe
Jean-Philippe Nougayrède
Robert Zumbihl
Alain Givaudan
Jean-Michel Escoubas
Eric Oswald
author_facet Grégory Jubelin
Carolina Varela Chavez
Frédéric Taieb
Mark J Banfield
Ascel Samba-Louaka
Rika Nobe
Jean-Philippe Nougayrède
Robert Zumbihl
Alain Givaudan
Jean-Michel Escoubas
Eric Oswald
author_sort Grégory Jubelin
collection DOAJ
description The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G(1) and G(2) cell cycle arrests, accumulation of the cyclin-dependent kinase inhibitors (CKIs) p21(waf1/cip1) and p27(kip1) and formation of actin stress fibres. The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad. Here we report the discovery and characterization of four Cif homologs encoded by different pathogenic or symbiotic bacteria isolated from vertebrates or invertebrates. Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli. Although these Cif homologs are remarkably divergent in primary sequence, the catalytic triad is strictly conserved and was shown to be crucial for cell cycle arrest, cytoskeleton reorganization and CKIs accumulation. These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans.
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spelling doaj-art-30dfdb9e288544338023102f97d781eb2025-08-20T02:00:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e485510.1371/journal.pone.0004855Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.Grégory JubelinCarolina Varela ChavezFrédéric TaiebMark J BanfieldAscel Samba-LouakaRika NobeJean-Philippe NougayrèdeRobert ZumbihlAlain GivaudanJean-Michel EscoubasEric OswaldThe cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G(1) and G(2) cell cycle arrests, accumulation of the cyclin-dependent kinase inhibitors (CKIs) p21(waf1/cip1) and p27(kip1) and formation of actin stress fibres. The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad. Here we report the discovery and characterization of four Cif homologs encoded by different pathogenic or symbiotic bacteria isolated from vertebrates or invertebrates. Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the beta-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli. Although these Cif homologs are remarkably divergent in primary sequence, the catalytic triad is strictly conserved and was shown to be crucial for cell cycle arrest, cytoskeleton reorganization and CKIs accumulation. These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004855&type=printable
spellingShingle Grégory Jubelin
Carolina Varela Chavez
Frédéric Taieb
Mark J Banfield
Ascel Samba-Louaka
Rika Nobe
Jean-Philippe Nougayrède
Robert Zumbihl
Alain Givaudan
Jean-Michel Escoubas
Eric Oswald
Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
PLoS ONE
title Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
title_full Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
title_fullStr Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
title_full_unstemmed Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
title_short Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.
title_sort cycle inhibiting factors cifs are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004855&type=printable
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