MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans

Mark Ramsdale, Laura Selway, David Andrew Stead, Janet Walker, Zhikang Yin, Susan Melanie Nicholls, Jonathan David Crowe, Alistair James Petersen Brown, Emma M. Sheils

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

MNL1, the Candida albicans homologue of an orphan Msn2-like gene (YER130c in Saccharomyces cerevisiae) has no known function. Here we report that MNL1 regulates weak acid stress responses. Deletion of MNL1 prevents the long-term adaptation of C. albicans cells to weak acid stresses and compromises their global transcriptional response under these conditions. The promoters of Mnl1-dependent genes contain a novel STRE-like element (SLE) that imposes Mnl1-dependent, weak acid stress-induced transcription upon a lacZ reporter in C. albicans. The SLE (HHYYCCCCTTYTY) is related to the Nrg1 response element (NRE) element recognized by the transcriptional repressor Nrg1. Deletion of NRG1 partially restores the ability of C. albicans mnl1 cells to adapt to weak acid stress, indicating that Mnl1 and Nrg1 act antagonistically to regulate this response. Molecular, microarray, and proteomic analyses revealed that Mnl1-dependent adaptation does not occur in cells exposed to proapoptotic or pronecrotic doses of weak acid, suggesting that Ras-pathway activation might suppress the Mnl1-dependent weak acid response in dying cells. Our work defines a role for this YER130c orthologue in stress adaptation and cell death.
Original languageEnglish
Pages (from-to)4393-4403
Number of pages11
JournalMolecular Biology of the Cell
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 2008

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Candida albicans
Acids
Response Elements
Microarray Analysis
Proteomics
Genes
Saccharomyces cerevisiae
Cell Death

Keywords

  • Actived protein kinase
  • Programmed cell death
  • saccharomyces cerevisiae
  • transcriptional response
  • gene expression
  • environmental changes
  • nuclear localization
  • phenotypic analysis
  • filamentous growth
  • ABC transporter

Cite this

MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans. / Ramsdale, Mark; Selway, Laura; Stead, David Andrew; Walker, Janet; Yin, Zhikang; Nicholls, Susan Melanie; Crowe, Jonathan David; Brown, Alistair James Petersen; Sheils, Emma M. .

In: Molecular Biology of the Cell, Vol. 19, No. 10, 10.2008, p. 4393-4403.

Research output: Contribution to journalArticle

Ramsdale, Mark ; Selway, Laura ; Stead, David Andrew ; Walker, Janet ; Yin, Zhikang ; Nicholls, Susan Melanie ; Crowe, Jonathan David ; Brown, Alistair James Petersen ; Sheils, Emma M. . / MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans. In: Molecular Biology of the Cell. 2008 ; Vol. 19, No. 10. pp. 4393-4403.
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