title: Mediator tail subunits can form amyloid-like aggregates in vivo and affect stress response in yeast.
abstract: The Med2, Med3 and Med15 proteins form a heterotrimeric subdomain in the budding yeast Mediator complex. This Med15 module is an important target for many gene specific transcription activators. A previous proteome wide screen in yeast identified Med3 as a protein with priogenic potential. In the present work, we have extended this observation and demonstrate that both Med3 and Med15 form amyloid-like protein aggregates under H2O2 stress conditions. Amyloid formation can also be stimulated by overexpression of Med3 or of a glutamine-rich domain present in Med15, which in turn leads to loss of the entire Med15 module from Mediator and a change in stress response. In combination with genome wide transcription analysis, our data demonstrate that amyloid formation can change the subunit composition of Mediator and thereby influence transcriptional output in budding yeast.
authors.affiliation: Institute of Biomedicine, University of Gothenburg, P.O. Box 440, SE-405 30 Göteborg, Sweden.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, SE-413 90 Göteborg, Sweden.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Biomedicine, University of Gothenburg, P.O. Box 440, SE-405 30 Göteborg, Sweden.
authors.forename: Jonas O P
authors.initials: JO
authors.lastname: Carlsten
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, SE-413 90 Göteborg, Sweden.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, SE-413 90 Göteborg, Sweden.
authors.forename: Junsheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, SE-413 90 Göteborg, Sweden.
authors.forename: Beidong
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Biomedicine, University of Gothenburg, P.O. Box 440, SE-405 30 Göteborg, Sweden claes.gustafsson@medkem.gu.se.
authors.forename: Claes M
authors.initials: CM
authors.lastname: Gustafsson
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D056892:Mediator Complex / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000682:Amyloid; C058337:GAL11 protein, S cerevisiae; D056892:Mediator Complex; C110281:PGD1 protein, S cerevisiae; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide