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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25741

Title: PKC Signaling Regulates Drug Resistance of Candida albicans and Saccharomyces cerevisiae via Divergent Circuitry Composed of the MAPK Cascade, Calcineurin and Hsp90
Authors: LaFayette, Shantelle
Advisor: Cowen, Leah
Department: Molecular and Medical Genetics
Keywords: Protein Kinase C
Drug Resistance
Candida albicans
Saccharomyces cerevisiae
Hsp90
Calcineurin
Issue Date: 7-Jan-2011
Abstract: Treating fungal infections is challenging due to the emergence of drug resistance and the limited number of clinically useful antifungal drugs. To improve clinical outcome it will be necessary to develop new antifungal drugs with different mechanisms of action and to discover drugs that improve the fungicidal activity of current antifungals. This study reveals a new role for fungal protein kinase C (PKC) signaling in resistance to drugs targeting the ergosterol biosynthesis pathway in the pathogenic fungus, Candida albicans, and the model yeast, Saccharomyces cerevisiae. PKC signaling enabled survival of antifungal-induced cell membrane stress in part through the mitogen-activated protein kinase (MAPK) cascade and through cross-talk with calcineurin signaling in both species. The molecular chaperone Hsp90, which stabilizes client proteins including calcineurin, also stabilized the terminal C. albicans MAPK, Mkc1. This establishes new circuitry connecting PKC with Hsp90 and calcineurin, and suggests that inhibiting fungal Pkc1 can be a promising strategy for treating life-threatening fungal infections.
URI: http://hdl.handle.net/1807/25741
Appears in Collections:Master
Department of Molecular Genetics - Master theses

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