Orphan quality control shapes network dynamics and gene expression.

Humans Gene Expression HEK293 Cells HeLa Cells Mutation Signal Transduction Transcription Factors / metabolism Ubiquitin-Protein Ligases / metabolism
MCRS1 MYC UBR5 branched ubiquitin chain orphan quality control proteasome stem cell transcription factor ubiquitin

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
03 08 2023
Historique:
received: 06 11 2022
revised: 13 04 2023
accepted: 21 06 2023
medline: 7 8 2023
pubmed: 22 7 2023
entrez: 21 7 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2023.06.015 PMID: 37478862
pubmed: 37478862
pii: S0092-8674(23)00691-8
doi: 10.1016/j.cell.2023.06.015
pii:
doi:

Substances chimiques

Transcription Factors 0
Ubiquitin-Protein Ligases EC 2.3.2.27
MYC protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

3460-3475.e23

Subventions

Organisme : NCRR NIH HHS
ID : S10 RR025622
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests M.R. is a co-founder and an SAB member of Nurix, Zenith, and Lyterian Therapeutics; an SAB member for Monte Rosa and Vicinitas Therapeutics; and an iPartner at The Column Group. N.H.T. receives funding from the Novartis Research Foundation and is an SAB member of Monte Rosa Therapeutics.

Auteurs

Kevin G Mark (KG)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

SriDurgaDevi Kolla (S)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

Jacob D Aguirre (JD)

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Danielle M Garshott (DM)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

Stefan Schmitt (S)

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Diane L Haakonsen (DL)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA, USA.

Christina Xu (C)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

Lukas Kater (L)

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Georg Kempf (G)

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Brenda Martínez-González (B)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

David Akopian (D)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.

Stephanie K See (SK)

Center for Emerging and Neglected Diseases, University of California at Berkeley, Berkeley, CA 94720, USA.

Nicolas H Thomä (NH)

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Electronic address: nicolas.thoma@fmi.ch.

Michael Rapé (M)

Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720, USA. Electronic address: mrape@berkeley.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HeLa › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Orphan quality control shapes network dynamics...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Orphan quality control shapes network dynamics...