title: The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activator of laccase in Cryptococcus neoformans.
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.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USA. szhang@uic.edu
authors.forename: Shirong
authors.initials: S
authors.lastname: Zhang
authors.forename: Moshe
authors.initials: M
authors.lastname: Hacham
authors.forename: John
authors.initials: J
authors.lastname: Panepinto
authors.forename: Guowu
authors.initials: G
authors.lastname: Hu
authors.forename: Soowan
authors.initials: S
authors.lastname: Shin
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.forename: Peter R
authors.initials: PR
authors.lastname: Williamson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D020862:GC Rich Sequence; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D042845:Laccase / Q000235:genetics*; D051379:Mice; D012045:Regulatory Sequences, Nucleic Acid; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014774:Virulence
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D014157:Transcription Factors; D003300:Copper; D007501:Iron; D042845:Laccase; D005947:Glucose; D002118:Calcium