Orphan quality control shapes network dynamics and gene expression
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
All eukaryotes require intricate protein networks to translate developmental signals into accurate cell fate decisions. Mutations that disturb interactions between network components often result in disease, but how the composition and dynamics of complex networks are established remains poorly understood. Here, we identify the E3 ligase UBR5 as a signaling hub that helps degrade unpaired subunits of multiple transcriptional regulators that act within a network centered on the c-Myc oncoprotein. Biochemical and structural analyses show that UBR5 binds motifs that only become available upon complex dissociation. By rapidly turning over unpaired transcription factor subunits, UBR5 establishes dynamic interactions between transcriptional regulators that allow cells to effectively execute gene expression while remaining receptive to environmental signals. We conclude that orphan quality control plays an essential role in establishing dynamic protein networks, which may explain the conserved need for protein degradation during transcription and offers opportunities to modulate gene expression in disease.
| Errataetall: |
ErratumIn: Cell. 2023 Sep 14;186(19):4252-4253. - PMID 37714136 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
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| Enthalten in: |
Cell - 186(2023), 16 vom: 03. Aug., Seite 3460-3475.e23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mark, Kevin G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.08.2023 Date Revised 15.09.2023 published: Print-Electronic ErratumIn: Cell. 2023 Sep 14;186(19):4252-4253. - PMID 37714136 Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2023.06.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a All eukaryotes require intricate protein networks to translate developmental signals into accurate cell fate decisions. Mutations that disturb interactions between network components often result in disease, but how the composition and dynamics of complex networks are established remains poorly understood. Here, we identify the E3 ligase UBR5 as a signaling hub that helps degrade unpaired subunits of multiple transcriptional regulators that act within a network centered on the c-Myc oncoprotein. Biochemical and structural analyses show that UBR5 binds motifs that only become available upon complex dissociation. By rapidly turning over unpaired transcription factor subunits, UBR5 establishes dynamic interactions between transcriptional regulators that allow cells to effectively execute gene expression while remaining receptive to environmental signals. We conclude that orphan quality control plays an essential role in establishing dynamic protein networks, which may explain the conserved need for protein degradation during transcription and offers opportunities to modulate gene expression in disease | ||
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| 700 | 1 | |a Kolla, SriDurgaDevi |e verfasserin |4 aut | |
| 700 | 1 | |a Aguirre, Jacob D |e verfasserin |4 aut | |
| 700 | 1 | |a Garshott, Danielle M |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitt, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Haakonsen, Diane L |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Kater, Lukas |e verfasserin |4 aut | |
| 700 | 1 | |a Kempf, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-González, Brenda |e verfasserin |4 aut | |
| 700 | 1 | |a Akopian, David |e verfasserin |4 aut | |
| 700 | 1 | |a See, Stephanie K |e verfasserin |4 aut | |
| 700 | 1 | |a Thomä, Nicolas H |e verfasserin |4 aut | |
| 700 | 1 | |a Rapé, Michael |e verfasserin |4 aut | |
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