Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1004630
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dc.titleCell Cycle-Independent Phospho-Regulation of Fkh2 during Hyphal Growth Regulates Candida albicans Pathogenesis
dc.contributor.authorGreig J.A.
dc.contributor.authorSudbery I.M.
dc.contributor.authorRichardson J.P.
dc.contributor.authorNaglik J.R.
dc.contributor.authorWang Y.
dc.contributor.authorSudbery P.E.
dc.date.accessioned2019-11-08T08:48:09Z
dc.date.available2019-11-08T08:48:09Z
dc.date.issued2015
dc.identifier.citationGreig J.A., Sudbery I.M., Richardson J.P., Naglik J.R., Wang Y., Sudbery P.E. (2015). Cell Cycle-Independent Phospho-Regulation of Fkh2 during Hyphal Growth Regulates Candida albicans Pathogenesis. PLoS Pathogens 11 (1) : 1-31. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1004630
dc.identifier.issn15537366
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161939
dc.description.abstractThe opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. In stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before START in the cell cycle, the phosphorylation profile is transformed before reverting to the yeast profile. This transformation does not occur when stationary phase cells are reinoculated into fresh medium supporting yeast growth. Mass spectrometry and mutational analyses identified residues phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non-phosphorylatable alanine altered the yeast phosphorylation profile and abrogated the characteristic transformation to the hyphal profile. Transcript profiling of the phosphorylation site mutant revealed that the hyphal phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes. Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3 in a phosphorylation-dependent manner, thereby providing a possible mechanism by which the phosphorylation of Fkh2 regulates its specificity. Thus, we have discovered a novel cell cycle-independent phospho-regulatory event that subverts a key component of the cell cycle machinery to a role in the switch from commensalism to pathogenicity. ? 2015 Greig et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectcell wall biosynthesis kinase 1
dc.subjectchromatin modifier Pob3
dc.subjectcyclin dependent kinase 28
dc.subjectcytokine
dc.subjectforkhead transcription factor
dc.subjectforkhead transcription factor 2
dc.subjectlactate dehydrogenase
dc.subjectpeptides and proteins
dc.subjecttranscriptome
dc.subjectunclassified drug
dc.subjectcell cycle protein
dc.subjectcyclin dependent kinase
dc.subjectforkhead transcription factor
dc.subjectfungal protein
dc.subjectArticle
dc.subjectbiofilm
dc.subjectCandida albicans
dc.subjectcell cycle progression
dc.subjectcell damage
dc.subjectdown regulation
dc.subjectfungus growth
dc.subjectgel electrophoresis
dc.subjectgene expression
dc.subjectgenetic transcription
dc.subjecthost parasite interaction
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmune response
dc.subjectmass spectrometry
dc.subjectmicroarray analysis
dc.subjectmicroscopy
dc.subjectmutational analysis
dc.subjectnonhuman
dc.subjectpathogenesis
dc.subjectplasmid
dc.subjectpolymerase chain reaction
dc.subjectprotein analysis
dc.subjectprotein phosphorylation
dc.subjectprotein processing
dc.subjectRNA isolation
dc.subjectWestern blotting
dc.subjectCandida albicans
dc.subjectcell cycle
dc.subjectfungus hyphae
dc.subjectgene expression profiling
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectgrowth, development and aging
dc.subjecthost pathogen interaction
dc.subjectmetabolism
dc.subjectpathogenicity
dc.subjectphosphorylation
dc.subjectphysiology
dc.subjectCandida albicans
dc.subjectCandida albicans
dc.subjectCell Cycle
dc.subjectCell Cycle Proteins
dc.subjectCyclin-Dependent Kinases
dc.subjectForkhead Transcription Factors
dc.subjectFungal Proteins
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Fungal
dc.subjectHost-Pathogen Interactions
dc.subjectHyphae
dc.subjectMicroarray Analysis
dc.subjectPhosphorylation
dc.subjectProtein Processing, Post-Translational
dc.typeArticle
dc.contributor.departmentBIOCHEMISTRY
dc.description.doi10.1371/journal.ppat.1004630
dc.description.sourcetitlePLoS Pathogens
dc.description.volume11
dc.description.issue1
dc.description.page1-31
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