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

Michelle Donna Leach, David Andrew Stead, Evelyn Ann Argo, Donna Margaret MacCallum, Alistair James Petersen Brown (Corresponding Author)

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Abstract

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.

Original languageEnglish
Pages (from-to)1574-1593
Number of pages20
JournalMolecular Microbiology
Volume79
Issue number6
Early online date26 Jan 2011
DOIs
Publication statusPublished - Mar 2011

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Ubiquitination
Candida albicans
Proteomics
Virulence
Polyubiquitin
Physiological Stress
Post Translational Protein Processing
Growth
Starvation
Cell Cycle Checkpoints
Cell Wall
Cell Cycle
Proteins
Fungi
Hot Temperature
Phenotype
Mutation

Cite this

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title = "Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans",
abstract = "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.",
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T1 - Molecular and proteomic analyses highlight the importance of ubiquitination for the stress resistance, metabolic adaptation, morphogenetic regulation and virulence of Candida albicans

AU - Leach, Michelle Donna

AU - Stead, David Andrew

AU - Argo, Evelyn Ann

AU - MacCallum, Donna Margaret

AU - Brown, Alistair James Petersen

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