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PMID:19818013

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Citation

Nicholls, S, Leach, MD, Priest, CL and Brown, AJ (2009) Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals. Mol. Microbiol. 74:844-61

Abstract

All organisms have evolved mechanisms that protect them against environmental stress. The major fungal pathogen of humans, Candida albicans, has evolved robust stress responses that protect it against human immune defences and promote its pathogenicity. However, C. albicans is unlikely to be exposed to heat shock as it is obligatorily associated with warm-blooded animals. Therefore, we examined the role of the heat shock transcription factor (Hsf1) in this pathogen. We show that C. albicans expresses an evolutionarily conserved Hsf1 (orf19.4775) that is phosphorylated in response to heat shock, induces transcription via the heat shock element (HSE), contributes to the global transcriptional response to heat shock, and is essential for viability. Why has Hsf1 been conserved in this obligate animal saprophyte? We reasoned that Hsf1 might contribute to medically relevant stress responses. However, this is not the case, as an Hsf1-specific HSE-lacZ reporter is not activated by oxidative, osmotic, weak acid or pH stress. Rather, Hsf1 is required for the expression of essential chaperones in the absence of heat shock (e.g. Hsp104, Hsp90, Hsp70). Furthermore, Hsf1 regulates the expression of HSE-containing genes in response to growth temperature in C. albicans. Therefore, the main role of Hsf1 in this pathogen might be the homeostatic modulation of chaperone levels in response to growth temperature, rather than the activation of acute responses to sudden thermal transitions.

Links

PubMed PMC3675641 Online version:10.1111/j.1365-2958.2009.06883.x

Keywords

Animals; Candida albicans/pathogenicity; Candida albicans/radiation effects; DNA-Binding Proteins/metabolism; Fungal Proteins/metabolism; Gene Expression Regulation, Fungal; Hot Temperature; Humans; Microbial Viability; Molecular Chaperones/biosynthesis; Phosphorylation; Stress, Physiological; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CANAL:Q5AQ33

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:Q5AQ33

involved_in

GO:0034605: cellular response to heat

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:Q5AQ33

part_of

GO:0005634: nucleus

ECO:0000305: curator inference used in manual assertion

GO:0045944

C

Seeded From UniProt

complete

CANAL:Q5AQ33

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000266: sequence orthology evidence used in manual assertion

SGD:S000003041

F

Seeded From UniProt

complete

See also

References

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