Role for the SCFCDC4 ubiquitin ligase in Candida albicans morphogenesis

Mol Biol Cell. 2005 Jun;16(6):2772-85. doi: 10.1091/mbc.e05-01-0079. Epub 2005 Apr 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Blotting, Western
  • Candida albicans / cytology
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Candida albicans / metabolism*
  • Epistasis, Genetic
  • Flow Cytometry
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Genes, Fungal
  • Ligases / metabolism*
  • Molecular Sequence Data
  • Morphogenesis / genetics
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Fungal Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Ligases