The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activator of laccase in Cryptococcus neoformans.
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.
Zhang
Shirong
S
Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USA. szhang@uic.edu
Hacham
Moshe
M
Panepinto
John
J
Hu
Guowu
G
Shin
Soowan
S
Zhu
Xudong
X
Williamson
Peter R
PR
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
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