Impact of the Unfolded Protein Response Upon Genome-Wide Expression Patterns, and the Role of Hac1 in the Polarized Growth, of Candida Albicans

Fungal Genet Biol. 2008 Sep;45(9):1235-47. doi: 10.1016/j.fgb.2008.06.001. Epub 2008 Jun 14.

Abstract

The unfolded protein response (UPR) regulates the expression of genes involved in the protein secretory pathway and in endoplasmic reticulum (ER) stress in yeasts and filamentous fungi. We have characterized the global transcriptional response of Candida albicans to ER stresses (dithiothreitol and tunicamycin) and established the impact of the transcription factor Hac1 upon this response. Expression of C. albicans Hac1, which is the functional homologue of Saccharomyces cerevisiae Hac1p, is predicted to be translationally regulated via an atypical mRNA splicing event during ER stress. C. albicans genes involved in secretion, vesicle trafficking, stress responses and cell wall biogenesis are up-regulated in response to ER stress, and translation and ribosome biogenesis genes are down-regulated. Hac1 is not essential for C. albicans viability, but plays a major role in this stress-related transcriptional response and is required for resistance to ER stress. In addition, we show that Hac1 plays an important role in regulating the morphology of C. albicans and in the expression of genes encoding cell surface proteins during ER stress, factors that are important in virulence of this fungal pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Candida albicans / drug effects
  • Candida albicans / genetics
  • Candida albicans / growth & development*
  • Candida albicans / physiology
  • Cell Polarity*
  • Cell Wall / genetics
  • Cell Wall / metabolism
  • Dithiothreitol / pharmacology
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / physiology
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Fungal
  • Genome, Fungal*
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Transcription, Genetic
  • Tunicamycin / pharmacology
  • Untranslated Regions

Substances

  • Fungal Proteins
  • Repressor Proteins
  • Untranslated Regions
  • Tunicamycin
  • Dithiothreitol