Abstract
The ability of transcriptional activation domains (TADs) to signal ubiquitin-mediated proteolysis suggests an involvement of the ubiquitin-proteasome pathway in transcription. To probe this involvement, we asked how ubiquitylation regulates the activity of a transcription factor containing the VP16 TAD. We show that the VP16 TAD signals ubiquitylation through the Met30 ubiquitin-ligase and that Met30 is also required for the VP16 TAD to activate transcription. The requirement for Met30 in transcription is circumvented by fusion of ubiquitin to the VP16 activator, demonstrating that activator ubiquitylation is essential for transcriptional activation. We propose that ubiquitylation regulates TAD function by serving as a dual signal for activation and activator destruction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism
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Cysteine Endopeptidases / metabolism
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DNA Replication
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F-Box Proteins
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Genes, Reporter
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Herpes Simplex Virus Protein Vmw65 / chemistry*
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Herpes Simplex Virus Protein Vmw65 / metabolism*
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Ligases / metabolism*
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Multienzyme Complexes / metabolism
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Promoter Regions, Genetic
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Proteasome Endopeptidase Complex
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Serine Endopeptidases / chemistry
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Serine Endopeptidases / metabolism
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Transcriptional Activation*
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Ubiquitin-Protein Ligase Complexes*
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Ubiquitin-Protein Ligases
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Ubiquitins / metabolism*
Substances
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Bacterial Proteins
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F-Box Proteins
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Herpes Simplex Virus Protein Vmw65
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LexA protein, Bacteria
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MET30 protein, S cerevisiae
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Multienzyme Complexes
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Recombinant Fusion Proteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Ubiquitins
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Ubiquitin-Protein Ligase Complexes
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Ubiquitin-Protein Ligases
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Serine Endopeptidases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Ligases