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Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor

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Abstract

Calcineurin is a phosphoprotein phosphatase devoted to the transduction of Ca2+-signals in eukaryotes. In the human pathogen Candida albicans, calcineurin function is required for cell morphogenesis, azole tolerance, membrane stress responses, survival in serum and virulence in mice. Molecular mechanisms as well as targets downstream C. albicans calcineurin involved in all these processes are still uncharacterized. Here we report the characterization of a C. albicans Crz1 calcineurin-regulated transcription factor using a Saccharomyces cerevisiae crz1Δ defective strain as heterologous host. CaCrz1p fulfils the function of its S. cerevisiae homolog protein to control the expression of several Ca2+/calcineurin-responsive genes acting on the CDRE sequence in promoters. In the model yeast, CaCrz1p activity and localization are regulated by calcineurin. Deletion of CRZ1 gene renders C. albicans hypersensitive to alkaline cations and membrane stress conditions, including that elicited by SDS and antifungal azoles. Our findings indicate that CaCrz1p is member of a calcium-regulated pathway required for the maintenance of membrane integrity.

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Acknowledgements

We are grateful to Profs. J. Pontón and M.D. Moragues for C. albicans strains, Prof. G. Quindós and M. Villar for help in drug susceptibility assays, E. Etxebarria for assistance in fluorescence microscopy and S. García for plasmid pDDB57. We thank M.J. Mazón, F. Portillo, and I. Mendizabal for comments and discussions. This work was supported by grants from Universidad del País Vasco (UPV/EHU 221.215-EA-8091/2000) and Gobierno Vasco (Etortek IE019-Biogune:Diamolfun) to I.F.L. and is dedicated to our colleague Prof. Cecilia Sarasola Yurrita.

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  1. Departamento de Química Aplicada, Facultad de Ciencias Químicas, Universidad del País Vasco (UPV/EHU), P° de Manuel de Lardizabal n°3, 20018, San Sebastián, Spain

    Mikel Santos & Iñigo F. de Larrinoa

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  1. Mikel Santos
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  2. Iñigo F. de Larrinoa
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Correspondence to Iñigo F. de Larrinoa.

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Communicated by J. Heitman

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Santos, M., de Larrinoa, I.F. Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor. Curr Genet 48, 88–100 (2005). https://doi.org/10.1007/s00294-005-0003-8

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