title: Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis.
abstract: Extracellular signal-regulated protein kinase (ERK, or mitogen-activated protein kinase [MAPK]) regulatory cascades in fungi turn on transcription factors that control developmental processes, stress responses, and cell wall integrity. CEK1 encodes a Candida albicans MAPK homolog (Cek1p), isolated by its ability to interfere with the Saccharomyces cerevisiae MAPK mating pathway. C. albicans cells with a deletion of the CEK1 gene are defective in shifting from a unicellular budding colonial growth mode to an agar-invasive hyphal growth mode when nutrients become limiting on solid medium with mannitol as a carbon source or on glucose when nitrogen is severely limited. The same phenotype is seen in C. albicans mutants in which the homologs (CST20, HST7, and CPH1) of the S. cerevisiae STE20, STE7, and STE12 genes are disrupted. In S. cerevisiae, the products of these genes function as part of a MAPK cascade required for mating and invasiveness of haploid cells and for pseudohyphal development of diploid cells. Epistasis studies revealed that the C. albicans CST20, HST7, CEK1, and CPH1 gene products lie in an equivalent, canonical, MAPK cascade. While Cek1p acts as part of the MAPK cascade involved in starvation-specific hyphal development, it may also play independent roles in C. albicans. In contrast to disruptions of the HST7 and CPH1 genes, disruption of the CEK1 gene adversely affects the growth of serum-induced mycelial colonies and attenuates virulence in a mouse model for systemic candidiasis.
authors.affiliation: Eukaryotic Genetics Group, National Research Council of Canada, Biotechnology Research Institute, Montreal, Quebec H4P 2R2.
authors.forename: C
authors.initials: C
authors.lastname: Csank
authors.forename: K
authors.initials: K
authors.lastname: Schröppel
authors.forename: E
authors.initials: E
authors.lastname: Leberer
authors.forename: D
authors.initials: D
authors.lastname: Harcus
authors.forename: O
authors.initials: O
authors.lastname: Mohamed
authors.forename: S
authors.initials: S
authors.lastname: Meloche
authors.forename: D Y
authors.initials: DY
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Whiteway
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000166:cytology / Q000254:growth & development* / Q000472:pathogenicity; D002177:Candidiasis / Q000401:mortality; D002454:Cell Differentiation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: C090837:CPH1 protein, Candida albicans; D005656:Fungal Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C077339:CEK1 protein, Candida albicans; D011494:Protein Kinases; C119859:CST20 protein, Candida albicans; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C119846:HST7 protein, Candida albicans; D020929:Mitogen-Activated Protein Kinase Kinases