Proteomics Links Ubiquitin Chain Topology Change to Transcription Factor Activation.
Mol Cell
; 76(1): 126-137.e7, 2019 10 03.
Article
em En
| MEDLINE
| ID: mdl-31444107
ABSTRACT
A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quantitative whole-proteome mass spectrometry to identify yeast proteins that are regulated by lysine 11 (K11)-linked ubiquitin chains. The entire Met4 pathway, which links cell proliferation with sulfur amino acid metabolism, was significantly affected by K11 chains and selected for mechanistic studies. Previously, we demonstrated that a K48-linked ubiquitin chain represses the transcription factor Met4. Here, we show that efficient Met4 activation requires a K11-linked topology. Mechanistically, our results propose that the K48 chain binds to a topology-selective tandem ubiquitin binding region in Met4 and competes with binding of the basal transcription machinery to the same region. The change to K11-enriched chain architecture releases this competition and permits binding of the basal transcription complex to activate transcription.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Transcrição Gênica
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Ativação Transcricional
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Proteínas de Saccharomyces cerevisiae
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Proteômica
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Fatores de Transcrição de Zíper de Leucina Básica
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Ubiquitinação
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2019
Tipo de documento:
Article