GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:23300438

From GONUTS
Jump to: navigation, search
Citation

Leach, MD, Budge, S, Walker, L, Munro, C, Cowen, LE and Brown, AJ (2012) Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast. PLoS Pathog. 8:e1003069

Abstract

Thermal adaptation is essential in all organisms. In yeasts, the heat shock response is commanded by the heat shock transcription factor Hsf1. Here we have integrated unbiased genetic screens with directed molecular dissection to demonstrate that multiple signalling cascades contribute to thermal adaptation in the pathogenic yeast Candida albicans. We show that the molecular chaperone heat shock protein 90 (Hsp90) interacts with and down-regulates Hsf1 thereby modulating short term thermal adaptation. In the longer term, thermal adaptation depends on key MAP kinase signalling pathways that are associated with cell wall remodelling: the Hog1, Mkc1 and Cek1 pathways. We demonstrate that these pathways are differentially activated and display cross talk during heat shock. As a result ambient temperature significantly affects the resistance of C. albicans cells to cell wall stresses (Calcofluor White and Congo Red), but not osmotic stress (NaCl). We also show that the inactivation of MAP kinase signalling disrupts this cross talk between thermal and cell wall adaptation. Critically, Hsp90 coordinates this cross talk. Genetic and pharmacological inhibition of Hsp90 disrupts the Hsf1-Hsp90 regulatory circuit thereby disturbing HSP gene regulation and reducing the resistance of C. albicans to proteotoxic stresses. Hsp90 depletion also affects cell wall biogenesis by impairing the activation of its client proteins Mkc1 and Hog1, as well as Cek1, which we implicate as a new Hsp90 client in this study. Therefore Hsp90 modulates the short term Hsf1-mediated activation of the classic heat shock response, coordinating this response with long term thermal adaptation via Mkc1- Hog1- and Cek1-mediated cell wall remodelling.

Links

PubMed PMC3531498 Online version:10.1371/journal.ppat.1003069

Keywords

Adaptation, Physiological; Candida albicans/metabolism; Cell Wall/metabolism; DNA-Binding Proteins/metabolism; Fungal Proteins/metabolism; Gene Expression Regulation; HSP90 Heat-Shock Proteins/metabolism; Heat-Shock Response; Hot Temperature; Mitogen-Activated Protein Kinase 3/metabolism; Mitogen-Activated Protein Kinases/metabolism; Transcription Factors/metabolism; Transcription, Genetic

Significance

Annotations

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

CANAL:HSP90

GO:0048523: negative regulation of cellular process

ECO:0000314:

P

Hsp90 in C. albicans down-regulates Hsp104 under heat shock conditions as shown in Figure 1. Hsp90 was depleted using doxycycline and mRNA levels were measured through Western Blot.

complete
CACAO 9296

CANAL:HSP90

GO:0080135: regulation of cellular response to stress

ECO:0000314:

P

Hsp90 in C. albicans regulates the stress response of the cells (heat shock and non-heat shock). In figure 8, Hsp90 was depleted from the cell using the drug doxycycline. When Hsp90 was depleted, the cells were less stress resistance. The stress resistance was measured by CFU (Colony-forming Unit) measurement.

complete
CACAO 9301

CANAL:Q5AQ33

GO:0048523: negative regulation of cellular process

ECO:0000314:

P

Hsf1 in C.albicans negatively regulates Hsp90 during heat shock. A Western Blot in Figure 1 showing heat shock induction and non-heat shock mRNA levels of Hsp90 in the presence of Hsf1

complete
CACAO 9292

CANAX:Q96W69

GO:0048523: negative regulation of cellular process

ECO:0000314:

P

Hsp90 in C. albicans down-regulates Hsp104 under heat shock conditions as shown in Figure 1. Hsp90 was depleted using doxycycline and mRNA levels were measured through Western Blot.

complete
CACAO 9297

See also

References

See Help:References for how to manage references in GONUTS.