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TitleOrphan quality control shapes network dynamics and gene expression.
Journal, issue, pagesCell, Vol. 186, Issue 16, Page 3460-3475.e23, Year 2023
Publish dateAug 3, 2023
AuthorsKevin G Mark / SriDurgaDevi Kolla / Jacob D Aguirre / Danielle M Garshott / Stefan Schmitt / Diane L Haakonsen / Christina Xu / Lukas Kater / Georg Kempf / Brenda Martínez-González / David Akopian / Stephanie K See / Nicolas H Thomä / Michael Rapé /
PubMed AbstractAll eukaryotes require intricate protein networks to translate developmental signals into accurate cell fate decisions. Mutations that disturb interactions between network components often result in ...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.
External linksCell / PubMed:37478862
MethodsEM (single particle)
Resolution4.45 Å
Structure data

EMDB-17541: Cryo-EM density map of UBR5 in complex with MCRS1
Method: EM (single particle) / Resolution: 4.45 Å

Source
  • Homo sapiens (human)

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