Differential Roles of Transcriptional Mediator Subunits in Regulation of Multidrug Resistance Gene Expression inSaccharomyces cerevisiae

Abstract

Med12 is a transcriptional Mediator subunit most typically associated with negative control of gene expression. Here Med12 is demonstrated to serve as a positive regulator required for activation of multidrug resistance gene expression in yeast cells lacking their mitochondrial genome.

Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata

“…C. glabrata contains two Gal11 homologues, one on chromosome 8 (CgGAL11A) and another on chromosome 6 (CgGAL11B). Our previous studies of S. cerevisiae have implicated the single Gal11 homologue present in the yeast as an important quantitative participant in 0 -mediated activation of ScPDR5 transcription (30). To determine if these C. glabrata homologues played a similar role in 0 induction of CgCDR1-CgPDR1 transcription, isogenic ϩ and 0 cells were constructed that lacked the CgGAL11 homologue on either chromosome 6 or chromosome 8.…”

Mediator Recruitment to Heat Shock Genes Requires Dual Hsf1 Activation Domains and Mediator Tail Subunits Med15 and Med16

“…The Tail, in particular a subcomplex termed the "Triad" (consisting of Med2, Med3, and Med15/Gal11), is a physical target of several yeast activators, including Gal4, Gcn4, Cha4, Pdr1, and Oaf1 (22)(23)(24)(25)(26)(27). Med15 is likewise targeted by several metazoan activators, such as the sterol regulatory element-binding protein (reviewed in Ref.…”

“…28), although it has also been implicated in positive regulation (29,30). The Kinase subunit Med12 serves as a target for the DNA-bound activator Pdr3 under conditions of mitochondrial stress in yeast (24) and is likewise a target of mammalian activators. Subunits located within the Head and Middle modules have also been implicated as activator targets (reviewed in Ref.…”

Análisis genético de la percepción del ácido salicílico en Arabidopsis thaliana. Caracterización de NRB4

“…But other functions include the use of fatty acids (see below) and the regulation of multidrug resistance (MDR). Thus, Δgal11 yeast does not grow in media with small amounts of ethidium bromide (Mylin et al 1991) or cycloheximide (Shahi et al 2010), while the wild type grows unaffected. This pathway is the same used by Candida glabrata to pump out of the cell ketoconazole (Thakur et al 2008).…”

“…GAL11 is the ortholog of MED15 in yeast, and the deletion of this gene is not lethal, but is essential for growth on nonfermentable carbon sources, for sporulation, and for mating (Mylin et al 1991, and references herein). The deletion of GAL11 renders yeast more sensitive to cycloheximide (Shahi et al 2010). Using this phenotype, we introduced NRB4 in yeast Δgal11, but it did not complement the growth in cycloheximide ( Figure S6E).…”