Regulation of the Candida albicans cell wall damage response by transcription factor Sko1 and PAS kinase Psk1

Mol Biol Cell. 2008 Jul;19(7):2741-51. doi: 10.1091/mbc.e08-02-0191. Epub 2008 Apr 23.

Abstract

The environmental niche of each fungus places distinct functional demands on the cell wall. Hence cell wall regulatory pathways may be highly divergent. We have pursued this hypothesis through analysis of Candida albicans transcription factor mutants that are hypersensitive to caspofungin, an inhibitor of beta-1,3-glucan synthase. We report here that mutations in SKO1 cause this phenotype. C. albicans Sko1 undergoes Hog1-dependent phosphorylation after osmotic stress, like its Saccharomyces cerevisiae orthologues, thus arguing that this Hog1-Sko1 relationship is conserved. However, Sko1 has a distinct role in the response to cell wall inhibition because 1) sko1 mutants are much more sensitive to caspofungin than hog1 mutants; 2) Sko1 does not undergo detectable phosphorylation in response to caspofungin; 3) SKO1 transcript levels are induced by caspofungin in both wild-type and hog1 mutant strains; and 4) sko1 mutants are defective in expression of caspofungin-inducible genes that are not induced by osmotic stress. Upstream Sko1 regulators were identified from a panel of caspofungin-hypersensitive protein kinase-defective mutants. Our results show that protein kinase Psk1 is required for expression of SKO1 and of Sko1-dependent genes in response to caspofungin. Thus Psk1 and Sko1 lie in a newly described signal transduction pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antifungal Agents / pharmacology
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / physiology*
  • Candida albicans / metabolism*
  • Caspofungin
  • Cell Wall
  • Echinocandins / pharmacology
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Fungal*
  • Lipopeptides
  • Models, Biological
  • Mutation
  • Osmosis
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*

Substances

  • Antifungal Agents
  • Basic-Leucine Zipper Transcription Factors
  • Echinocandins
  • Lipopeptides
  • Repressor Proteins
  • SKO1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Protein Kinases
  • PSK1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • Caspofungin