Role for the SCFCDC4 Ubiquitin Ligase in Candida albicans Morphogenesis

摘要

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 Ca CDC4 , a homologue of the Saccharomyces cerevisiae F-box protein component of the SCFCDC4 ubiquitin ligase, is viable and displays constitutive filamentous, mostly hyphal, growth. The phenotype of the Ca cdc4 – / – 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 SCFCaCDC4. Epistasis analysis indicates that the Ca cdc4 – / – 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 SCFCDC4 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 Ca cdc4 – / – mutant. However, ectopic expression and deletion of SOL1 indicate a role for this gene in C . albicans morphogenesis.