Global role of the protein kinase Gcn2 in the human pathogen Candida albicans

Eukaryot Cell. 2005 Oct;4(10):1687-96. doi: 10.1128/EC.4.10.1687-1696.2005.

Abstract

The pathogen Candida albicans responds to amino acid starvation by activating pseudohyphal development and the expression of amino acid biosynthetic genes (GCN response). In Saccharomyces cerevisiae, the GCN response is dependent on Gcn2, which regulates the translation of the transcription factor Gcn4. Therefore, we examined the role of Gcn2 in C. albicans by using molecular, cellular, and genomic approaches. We show that C. albicans GCN2 encodes an eIF2alpha kinase, like its S. cerevisiae homologue. However, GCN4 appears to be regulated mainly at the transcriptional level in C. albicans. Furthermore, the inactivation of C. albicans Gcn2 only partially attenuates growth under amino acid starvation conditions and resistance to the histidine analogue 3-aminotriazole. Our comparison of the Gcn4 and Gcn2 regulons by transcript profiling reinforces the view that Gcn2 contributes to, but is not essential for, the activation of general amino acid control in C. albicans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Amitrole / pharmacology
  • Animals
  • Basic-Leucine Zipper Transcription Factors
  • Candida albicans / cytology
  • Candida albicans / drug effects
  • Candida albicans / enzymology*
  • Candida albicans / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases
  • Regulon
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Amino Acids
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Fungal Proteins
  • GCN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Protein Kinases
  • GCN2 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Amitrole