title: MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans.
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.
authors.affiliation: Institute of Medical Sciences, School of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom. m.ramsdale@exeter.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Ramsdale
authors.forename: Laura
authors.initials: L
authors.lastname: Selway
authors.forename: David
authors.initials: D
authors.lastname: Stead
authors.forename: Jan
authors.initials: J
authors.lastname: Walker
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Yin
authors.forename: Susan M
authors.initials: SM
authors.lastname: Nicholls
authors.forename: Jonathan
authors.initials: J
authors.lastname: Crowe
authors.forename: Emma M
authors.initials: EM
authors.lastname: Sheils
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D020890:Neuregulin-1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D040901:Proteomics / Q000379:methods; D043323:alpha-Mannosidase / Q000378:metabolism*
chemical_list: D020890:Neuregulin-1; D043323:alpha-Mannosidase; D019342:Acetic Acid