Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.

The cycle inhibiting factors (Cif), produced by pathogenic bacteria isolated from vertebrates and invertebrates, belong to a family of molecules called cyclomodulins that interfere with the eukaryotic cell cycle. Cif blocks the cell cycle at both the G₁/S and G₂/M transitions by inducing the stabili...

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Autores principales:	Grégory Jubelin, Frédéric Taieb, David M Duda, Yun Hsu, Ascel Samba-Louaka, Rika Nobe, Marie Penary, Claude Watrin, Jean-Philippe Nougayrède, Brenda A Schulman, C Erec Stebbins, Eric Oswald
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ffc0c089152b4d21b4a09b0efdf3bbd2
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spelling	oai:doaj.org-article:ffc0c089152b4d21b4a09b0efdf3bbd22021-11-18T06:03:52ZPathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.1553-73661553-737410.1371/journal.ppat.1001128https://doaj.org/article/ffc0c089152b4d21b4a09b0efdf3bbd22010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20941356/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The cycle inhibiting factors (Cif), produced by pathogenic bacteria isolated from vertebrates and invertebrates, belong to a family of molecules called cyclomodulins that interfere with the eukaryotic cell cycle. Cif blocks the cell cycle at both the G₁/S and G₂/M transitions by inducing the stabilization of cyclin-dependent kinase inhibitors p21(waf1) and p27(kip1). Using yeast two-hybrid screens, we identified the ubiquitin-like protein NEDD8 as a target of Cif. Cif co-compartmentalized with NEDD8 in the host cell nucleus and induced accumulation of NEDD8-conjugated cullins. This accumulation occurred early after cell infection and correlated with that of p21 and p27. Co-immunoprecipitation revealed that Cif interacted with cullin-RING ubiquitin ligase complexes (CRLs) through binding with the neddylated forms of cullins 1, 2, 3, 4A and 4B subunits of CRL. Using an in vitro ubiquitylation assay, we demonstrate that Cif directly inhibits the neddylated CUL1-associated ubiquitin ligase activity. Consistent with this inhibition and the interaction of Cif with several neddylated cullins, we further observed that Cif modulates the cellular half-lives of various CRL targets, which might contribute to the pathogenic potential of diverse bacteria.Grégory JubelinFrédéric TaiebDavid M DudaYun HsuAscel Samba-LouakaRika NobeMarie PenaryClaude WatrinJean-Philippe NougayrèdeBrenda A SchulmanC Erec StebbinsEric OswaldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 9, p e1001128 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Grégory Jubelin Frédéric Taieb David M Duda Yun Hsu Ascel Samba-Louaka Rika Nobe Marie Penary Claude Watrin Jean-Philippe Nougayrède Brenda A Schulman C Erec Stebbins Eric Oswald Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.
description	The cycle inhibiting factors (Cif), produced by pathogenic bacteria isolated from vertebrates and invertebrates, belong to a family of molecules called cyclomodulins that interfere with the eukaryotic cell cycle. Cif blocks the cell cycle at both the G₁/S and G₂/M transitions by inducing the stabilization of cyclin-dependent kinase inhibitors p21(waf1) and p27(kip1). Using yeast two-hybrid screens, we identified the ubiquitin-like protein NEDD8 as a target of Cif. Cif co-compartmentalized with NEDD8 in the host cell nucleus and induced accumulation of NEDD8-conjugated cullins. This accumulation occurred early after cell infection and correlated with that of p21 and p27. Co-immunoprecipitation revealed that Cif interacted with cullin-RING ubiquitin ligase complexes (CRLs) through binding with the neddylated forms of cullins 1, 2, 3, 4A and 4B subunits of CRL. Using an in vitro ubiquitylation assay, we demonstrate that Cif directly inhibits the neddylated CUL1-associated ubiquitin ligase activity. Consistent with this inhibition and the interaction of Cif with several neddylated cullins, we further observed that Cif modulates the cellular half-lives of various CRL targets, which might contribute to the pathogenic potential of diverse bacteria.
format	article
author	Grégory Jubelin Frédéric Taieb David M Duda Yun Hsu Ascel Samba-Louaka Rika Nobe Marie Penary Claude Watrin Jean-Philippe Nougayrède Brenda A Schulman C Erec Stebbins Eric Oswald
author_facet	Grégory Jubelin Frédéric Taieb David M Duda Yun Hsu Ascel Samba-Louaka Rika Nobe Marie Penary Claude Watrin Jean-Philippe Nougayrède Brenda A Schulman C Erec Stebbins Eric Oswald
author_sort	Grégory Jubelin
title	Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.
title_short	Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.
title_full	Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.
title_fullStr	Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.
title_full_unstemmed	Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.
title_sort	pathogenic bacteria target nedd8-conjugated cullins to hijack host-cell signaling pathways.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/ffc0c089152b4d21b4a09b0efdf3bbd2
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Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways.

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