Good fungi gone bad: the corruption of calcineurin.

Published

Journal Article (Review)

Calcineurin is a Ca(2+)/calmodulin-activated protein phosphatase that is conserved in eukaryotes, from yeast to humans, and is the conserved target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. Genetic studies in yeast and fungi established the molecular basis of calcineurin inhibition by the cyclophilin A-CsA and FKBP12-FK506 complexes. Calcineurin also functions in fungi to control a myriad of physiological processes including cell cycle progression, cation homeostasis, and morphogenesis. Recent investigations into the molecular mechanisms of pathogenesis in Candida albicans and Cryptococcus neoformans, two fungi that cause life-threatening infections in humans, have revealed an essential role for calcineurin in morphogenesis, virulence, and antifungal drug action. Novel non-immunosuppressive analogs of the calcineurin inhibitors CsA and FK506 that retain antifungal activity have been identified and hold promise as candidate antifungal drugs. In addition, comparisons of calcineurin function in both fungi and humans may identify fungal-specific components of calcineurin-signaling pathways that could be targeted for therapy, as well as conserved elements of calcium signaling events.

Full Text

Duke Authors

Cited Authors

  • Fox, DS; Heitman, J

Published Date

  • October 2002

Published In

Volume / Issue

  • 24 / 10

Start / End Page

  • 894 - 903

PubMed ID

  • 12325122

Pubmed Central ID

  • 12325122

International Standard Serial Number (ISSN)

  • 0265-9247

Digital Object Identifier (DOI)

  • 10.1002/bies.10157

Language

  • eng

Conference Location

  • United States