Role for the SCFCDC4 ubiquitin ligase in Candida albicans morphogenesis.
The ability of Candida albicans, a major fungal pathogen, to switch between a yeast form, and a hyphal (mold) form is recognized as being important for the ability of the organism to invade the host and cause disease. We found that a C. albicans mutant deleted for CaCDC4, a homologue of the Saccharomyces cerevisiae F-box protein component of the SCF(CDC4) ubiquitin ligase, is viable and displays constitutive filamentous, mostly hyphal, growth. The phenotype of the Cacdc4-/- mutant suggests that ubiquitin-mediated protein degradation is involved in the regulation of the dimorphic switch of C. albicans and that one or more regulators of the yeast-to-mold switch are among the substrates of SCF(CaCDC4). Epistasis analysis indicates that the Cacdc4-/- phenotype is largely independent of the filamentation-inducing transcription factors Efg1 and Cph1. We identify C. albicans Far1 and Sol1, homologues of the S. cerevisiae SCF(CDC4) substrates Far1 and Sic1, and show that Sol1 is a substrate of C. albicans Cdc4. Neither protein is essential for the hyphal phenotype of the Cacdc4-/- mutant. However, ectopic expression and deletion of SOL1 indicate a role for this gene in C. albicans morphogenesis.
Atir-Lande
Avigail
A
Department of Molecular Microbiology, B. Rappaport Faculty of Medicine, Technion-IIT, and the Rappaport Institute for Research in the Medical Sciences, Haifa 31096, Israel.
Gildor
Tsvia
T
Kornitzer
Daniel
D
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002176:Candida albicans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004843:Epistasis, Genetic; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal; D008025:Ligases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D008025:Ligases