The Hsp70 Member, Ssa1, Acts as a DNA-binding Transcriptional Co-Activator of Laccase in Cryptococcus Neoformans

Mol Microbiol. 2006 Nov;62(4):1090-101. doi: 10.1111/j.1365-2958.2006.05422.x. Epub 2006 Oct 16.

Abstract

Hsp70 proteins are a well-known class of chaperones that have also been described to have roles in cellular regulation. Here, we show that a Cryptococcus neoformans Hsp70 homologue Ssa1 acts as a DNA-binding transcriptional co-activator of the fungal virulence factor, laccase, via binding to a GC-rich element within the 5'-UAS in response to glucose starvation, iron, copper, calcium and temperature. In addition, Ssa1 forms a regulatory complex with heat shock transcription factor and TATA-binding protein during laccase induction. Furthermore, deletion of Ssa1 results in reduced laccase and attenuated virulence using a mouse model. These results indicate that Hsp70 functions as a stress-related transcriptional co-activator required for fungal virulence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Copper / metabolism
  • Cryptococcosis / microbiology
  • Cryptococcus neoformans / enzymology*
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / pathogenicity
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • GC Rich Sequence
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Fungal
  • Glucose / metabolism
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / physiology*
  • Iron / metabolism
  • Laccase / genetics*
  • Mice
  • Regulatory Sequences, Nucleic Acid
  • Temperature
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation
  • Virulence

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • Transcription Factors
  • Copper
  • Iron
  • Laccase
  • Glucose
  • Calcium