Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pbio.1001290
Title: Mediator acts upstream of the transcriptional activator Gal4
Authors: Ang K.
Ee G.
Ang E.
Koh E.
Siew W.L.
Chan Y.M.
Nur S.
Tan Y.S.
Lehming N. 
Keywords: F box protein
Gal80 protein
galactose
glucose
protein
protein kinase
protein kinase Snf1
RNA polymerase
transcription factor GAL4
ubiquitin
ubiquitin protein ligase E3
unclassified drug
cycline
DNA binding protein
F box protein
GAL4 protein, S cerevisiae
GAL80 protein, S cerevisiae
galactose
Mdm30 protein, S cerevisiae
MED21 protein, human
mediator complex
repressor protein
S phase kinase associated protein
Saccharomyces cerevisiae protein
SKP1 protein, human
SSN8 protein, S cerevisiae
transcription factor
ubiquitin
article
controlled study
DNA sequence
gene control
gene deletion
gene expression
gene function
gene mutation
genetic code
mutagenesis
nonhuman
promoter region
protein degradation
protein protein interaction
Saccharomyces cerevisiae
culture medium
fungal gene
gene expression regulation
genetic transfection
genetics
HeLa cell
human
immunoprecipitation
metabolism
protein binding
protein stability
Saccharomyces cerevisiae
signal transduction
transcription initiation
Culture Media
Cyclins
DNA-Binding Proteins
F-Box Proteins
Galactose
Gene Deletion
Gene Expression Regulation, Fungal
Genes, Fungal
HeLa Cells
Humans
Immunoprecipitation
Mediator Complex
Promoter Regions, Genetic
Protein Binding
Protein Stability
Proteolysis
Repressor Proteins
S-Phase Kinase-Associated Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Signal Transduction
Transcription Factors
Transcriptional Activation
Transfection
Ubiquitin
Issue Date: 2012
Publisher: Public Library of Science
Citation: Ang 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
Abstract: The 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.
Source Title: PLoS Biology
URI: https://scholarbank.nus.edu.sg/handle/10635/165408
ISSN: 15449173
DOI: 10.1371/journal.pbio.1001290
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