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
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Calcium / metabolism
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Copper / metabolism
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Cryptococcosis / microbiology
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Cryptococcus neoformans / enzymology*
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Cryptococcus neoformans / genetics
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Cryptococcus neoformans / pathogenicity
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Fungal Proteins / genetics
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Fungal Proteins / physiology*
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GC Rich Sequence
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Fungal
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Glucose / metabolism
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / physiology*
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Iron / metabolism
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Laccase / genetics*
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Mice
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Regulatory Sequences, Nucleic Acid
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Temperature
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcriptional Activation
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Virulence
Substances
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DNA-Binding Proteins
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Fungal Proteins
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HSP70 Heat-Shock Proteins
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Transcription Factors
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Copper
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Iron
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Laccase
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Glucose
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Calcium