Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans

Post-translational modifications of proteins play key roles in eukaryotic growth, differentiation and environmental adaptation. In model systems the ubiquitination of specific proteins contributes to the control of cell cycle progression, stress adaptation and metabolic reprogramming. We have combin...

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Main Authors:	Leach, Michelle D, Stead, David A, Argo, Evelyn, MacCallum, Donna M, Brown, Alistair J P
Format:	Online
Language:	English
Published:	Blackwell Publishing Ltd 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084552/

id	pubmed-3084552
recordtype	oai_dc
spelling	pubmed-30845522011-05-11 Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans Leach, Michelle D Stead, David A Argo, Evelyn MacCallum, Donna M Brown, Alistair J P Research Articles Post-translational modifications of proteins play key roles in eukaryotic growth, differentiation and environmental adaptation. In model systems the ubiquitination of specific proteins contributes to the control of cell cycle progression, stress adaptation and metabolic reprogramming. We have combined molecular, cellular and proteomic approaches to examine the roles of ubiquitination in Candida albicans, because little is known about ubiquitination in this major fungal pathogen of humans. Independent null (ubi4/ubi4) and conditional (MET3p-UBI4/ubi4) mutations were constructed at the C. albicans polyubiquitin-encoding locus. These mutants displayed morphological and cell cycle defects, as well as sensitivity to thermal, oxidative and cell wall stresses. Furthermore, ubi4/ubi4 cells rapidly lost viability under starvation conditions. Consistent with these phenotypes, proteins with roles in stress responses (Gnd1, Pst2, Ssb1), metabolism (Acs2, Eno1, Fba1, Gpd2, Pdx3, Pgk1, Tkl1) and ubiquitination (Ubi4, Ubi3, Pre1, Pre3, Rpt5) were among the ubiquitination targets we identified, further indicating that ubiquitination plays key roles in growth, stress responses and metabolic adaptation in C. albicans. Clearly ubiquitination plays key roles in the regulation of fundamental cellular processes that underpin the pathogenicity of this medically important fungus. This was confirmed by the observation that the virulence of C. albicans ubi4/ubi4 cells is significantly attenuated. Blackwell Publishing Ltd 2011-03 /pmc/articles/PMC3084552/ /pubmed/21269335 http://dx.doi.org/10.1111/j.1365-2958.2011.07542.x Text en Copyright © 2011 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Leach, Michelle D Stead, David A Argo, Evelyn MacCallum, Donna M Brown, Alistair J P
spellingShingle	Leach, Michelle D Stead, David A Argo, Evelyn MacCallum, Donna M Brown, Alistair J P Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans
author_facet	Leach, Michelle D Stead, David A Argo, Evelyn MacCallum, Donna M Brown, Alistair J P
author_sort	Leach, Michelle D
title	Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans
title_short	Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans
title_full	Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans
title_fullStr	Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans
title_full_unstemmed	Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans
title_sort	molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of candida albicans
description	Post-translational modifications of proteins play key roles in eukaryotic growth, differentiation and environmental adaptation. In model systems the ubiquitination of specific proteins contributes to the control of cell cycle progression, stress adaptation and metabolic reprogramming. We have combined molecular, cellular and proteomic approaches to examine the roles of ubiquitination in Candida albicans, because little is known about ubiquitination in this major fungal pathogen of humans. Independent null (ubi4/ubi4) and conditional (MET3p-UBI4/ubi4) mutations were constructed at the C. albicans polyubiquitin-encoding locus. These mutants displayed morphological and cell cycle defects, as well as sensitivity to thermal, oxidative and cell wall stresses. Furthermore, ubi4/ubi4 cells rapidly lost viability under starvation conditions. Consistent with these phenotypes, proteins with roles in stress responses (Gnd1, Pst2, Ssb1), metabolism (Acs2, Eno1, Fba1, Gpd2, Pdx3, Pgk1, Tkl1) and ubiquitination (Ubi4, Ubi3, Pre1, Pre3, Rpt5) were among the ubiquitination targets we identified, further indicating that ubiquitination plays key roles in growth, stress responses and metabolic adaptation in C. albicans. Clearly ubiquitination plays key roles in the regulation of fundamental cellular processes that underpin the pathogenicity of this medically important fungus. This was confirmed by the observation that the virulence of C. albicans ubi4/ubi4 cells is significantly attenuated.
publisher	Blackwell Publishing Ltd
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084552/
_version_	1611451069892657152

Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans

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