Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pbio.1001290
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dc.titleMediator acts upstream of the transcriptional activator Gal4
dc.contributor.authorAng K.
dc.contributor.authorEe G.
dc.contributor.authorAng E.
dc.contributor.authorKoh E.
dc.contributor.authorSiew W.L.
dc.contributor.authorChan Y.M.
dc.contributor.authorNur S.
dc.contributor.authorTan Y.S.
dc.contributor.authorLehming N.
dc.date.accessioned2020-03-13T05:26:07Z
dc.date.available2020-03-13T05:26:07Z
dc.date.issued2012
dc.identifier.citationAng K., Ee G., Ang E., Koh E., Siew W.L., Chan Y.M., Nur S., Tan Y.S., Lehming N. (2012). Mediator acts upstream of the transcriptional activator Gal4. PLoS Biology 10 (3) : e1001290. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pbio.1001290
dc.identifier.issn15449173
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165408
dc.description.abstractThe proteasome inhibitor MG132 had been shown to prevent galactose induction of the S. cerevisiae GAL1 gene, demonstrating that ubiquitin proteasome-dependent degradation of transcription factors plays an important role in the regulation of gene expression. The deletion of the gene encoding the F-box protein Mdm30 had been reported to stabilize the transcriptional activator Gal4 under inducing conditions and to lead to defects in galactose utilization, suggesting that recycling of Gal4 is required for its function. Subsequently, however, it was argued that Gal4 remains stably bound to the enhancer under inducing conditions, suggesting that proteolytic turnover of Gal4 might not be required for its function. We have performed an alanine-scanning mutagenesis of ubiquitin and isolated a galactose utilization-defective ubiquitin mutant. We have used it for an unbiased suppressor screen and identified the inhibitor Gal80 as a suppressor of the transcriptional defects of the ubiquitin mutant, indicating that the protein degradation of the inhibitor Gal80, and not of the activator Gal4, is required for galactose induction of the GAL genes. We also show that in the absence of Gal80, Mdm30 is not required for Gal4 function, strongly supporting this hypothesis. Furthermore, we have found that Mediator controls the galactose-induced protein degradation of Gal80, which places Mediator genetically upstream of the activator Gal4. Mediator had originally been isolated by its ability to respond to transcriptional activators, and here we have discovered a leading role for Mediator in the process of transcription. The protein kinase Snf1 senses the inducing conditions and transduces the signal to Mediator, which initiates the degradation of the inhibitor Gal80 with the help of the E3 ubiquitin ligase SCF Mdm30. The ability of Mediator to control the protein degradation of transcriptional inhibitors indicates that Mediator is actually able to direct its own recruitment to gene promoters. © 2012 Ang et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectF box protein
dc.subjectGal80 protein
dc.subjectgalactose
dc.subjectglucose
dc.subjectprotein
dc.subjectprotein kinase
dc.subjectprotein kinase Snf1
dc.subjectRNA polymerase
dc.subjecttranscription factor GAL4
dc.subjectubiquitin
dc.subjectubiquitin protein ligase E3
dc.subjectunclassified drug
dc.subjectcycline
dc.subjectDNA binding protein
dc.subjectF box protein
dc.subjectGAL4 protein, S cerevisiae
dc.subjectGAL80 protein, S cerevisiae
dc.subjectgalactose
dc.subjectMdm30 protein, S cerevisiae
dc.subjectMED21 protein, human
dc.subjectmediator complex
dc.subjectrepressor protein
dc.subjectS phase kinase associated protein
dc.subjectSaccharomyces cerevisiae protein
dc.subjectSKP1 protein, human
dc.subjectSSN8 protein, S cerevisiae
dc.subjecttranscription factor
dc.subjectubiquitin
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectDNA sequence
dc.subjectgene control
dc.subjectgene deletion
dc.subjectgene expression
dc.subjectgene function
dc.subjectgene mutation
dc.subjectgenetic code
dc.subjectmutagenesis
dc.subjectnonhuman
dc.subjectpromoter region
dc.subjectprotein degradation
dc.subjectprotein protein interaction
dc.subjectSaccharomyces cerevisiae
dc.subjectculture medium
dc.subjectfungal gene
dc.subjectgene expression regulation
dc.subjectgenetic transfection
dc.subjectgenetics
dc.subjectHeLa cell
dc.subjecthuman
dc.subjectimmunoprecipitation
dc.subjectmetabolism
dc.subjectprotein binding
dc.subjectprotein stability
dc.subjectSaccharomyces cerevisiae
dc.subjectsignal transduction
dc.subjecttranscription initiation
dc.subjectCulture Media
dc.subjectCyclins
dc.subjectDNA-Binding Proteins
dc.subjectF-Box Proteins
dc.subjectGalactose
dc.subjectGene Deletion
dc.subjectGene Expression Regulation, Fungal
dc.subjectGenes, Fungal
dc.subjectHeLa Cells
dc.subjectHumans
dc.subjectImmunoprecipitation
dc.subjectMediator Complex
dc.subjectPromoter Regions, Genetic
dc.subjectProtein Binding
dc.subjectProtein Stability
dc.subjectProteolysis
dc.subjectRepressor Proteins
dc.subjectS-Phase Kinase-Associated Proteins
dc.subjectSaccharomyces cerevisiae
dc.subjectSaccharomyces cerevisiae Proteins
dc.subjectSignal Transduction
dc.subjectTranscription Factors
dc.subjectTranscriptional Activation
dc.subjectTransfection
dc.subjectUbiquitin
dc.typeArticle
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.description.doi10.1371/journal.pbio.1001290
dc.description.sourcetitlePLoS Biology
dc.description.volume10
dc.description.issue3
dc.description.pagee1001290
dc.published.statePublished
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