title: Elucidating the response of Kluyveromyces lactis to arsenite and peroxide stress and the role of the transcription factor KlYap8.
abstract: All organisms need to sense and respond to a range of stress conditions. In this study, we used transcriptional profiling to identify genes and cellular processes that are responsive during arsenite and tert-butyl hydroperoxide exposure in Kluyveromyces lactis. Many arsenite-responsive genes encode proteins involved in redox processes, protein folding and stabilization, and transmembrane transport. The majority of peroxide-responsive genes encode functions related to transcription, translation, redox processes, metabolism and transport. A substantial number of these stress-regulated genes contain binding motifs for the AP-1 like transcription factors KlYap1 and KlYap8. We demonstrate that KlYap8 binds to and regulates gene expression through a 13 base-pair promoter motif, and that KlYap8 provides protection against arsenite, antimonite, cadmium and peroxide toxicity. Direct transport assays show that Klyap8Δ cells accumulate more arsenic and cadmium than wild type cells and that the Klyap8Δ mutant is defective in arsenic and cadmium export. KlYap8 regulates gene expression in response to both arsenite and peroxide, and might cooperate with KlYap1 in regulation of specific gene targets. Comparison of KlYap8 with its Saccharomyces cerevisiae orthologue ScYap8 indicates that KlYap8 senses and responds to multiple stress signals whereas ScYap8 is only involved in the response to arsenite and antimonite. Thus, our data suggest that functional specialization of ScYap8 has occurred after the whole genome duplication event. This is the first genome-wide stress response analysis in K. lactis and the first demonstration of KlYap8 function.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-405 30 Göteborg, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Veide Vilg
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-405 30 Göteborg, Sweden.
authors.forename: Nallani Vijay
authors.initials: NV
authors.lastname: Kumar
authors.affiliation: Institute of Experimental Biology, University of Wroclaw, Kanonia 6/8, 50-328 Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Maciaszczyk-Dziubinska
authors.affiliation: Institute of Experimental Biology, University of Wroclaw, Kanonia 6/8, 50-328 Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sloma
authors.affiliation: INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech, UMR Micalis, F-78350 Jouy-en-Josas, France.
authors.forename: Djamila
authors.initials: D
authors.lastname: Onesime
authors.affiliation: AgroParisTech, UMR 518 MIA, F-75005 Paris, France; INRA, UMR 518 MIA, F-75005 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Aubert
authors.affiliation: Institute of Experimental Biology, University of Wroclaw, Kanonia 6/8, 50-328 Wroclaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Migocka
authors.affiliation: Institute of Experimental Biology, University of Wroclaw, Kanonia 6/8, 50-328 Wroclaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Wysocki
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-405 30 Göteborg, Sweden. Electronic address: markus.tamas@cmb.gu.se.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Tamás
mesh_terms: D018053:Arsenites / Q000494:pharmacology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007716:Kluyveromyces / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*; D059467:Transcriptome
chemical_list: D018053:Arsenites; D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; D006861:Hydrogen Peroxide; C015001:arsenite
keywords: AP-1 protein; Arsenic; Metalloid; Oxidative stress; Transcription factor; Yeast