Dataset Information

Orphan quality control shapes network dynamics and gene expression

ABSTRACT: 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 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 orphan 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 unique opportunities to modulate gene expression in disease. Crosslinking mass spec experiment with UBR5 HECT domain STREP-SUMO-MCRS1 and DSSO.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jan Seebacher

LAB HEAD: Nicolas Holger Thoma

PROVIDER: PXD041519 | Pride | 2023-05-30

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	E4_230324_JS_UBR5_L_MCRS1_1p6mM_DSSO_S02_FAIMS_5uL_01.csv	Csv
	E4_230324_JS_UBR5_L_MCRS1_1p6mM_DSSO_S02_FAIMS_5uL_01.fasta	Fasta
	E4_230324_JS_UBR5_L_MCRS1_1p6mM_DSSO_S02_FAIMS_5uL_01.raw	Raw
	E4_230324_JS_UBR5_L_MCRS1_1p6mM_DSSO_S02_FAIMS_5uL_01_CSMs.txt	Txt
	E4_230324_JS_UBR5_L_MCRS1_1p6mM_DSSO_S02_FAIMS_5uL_01_Crosslinks.txt	Txt

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Publications

Orphan quality control shapes network dynamics and gene expression.

Mark Kevin G KG Kolla SriDurgaDevi S Aguirre Jacob D JD Garshott Danielle M DM Schmitt Stefan S Haakonsen Diane L DL Xu Christina C Kater Lukas L Kempf Georg G Martínez-González Brenda B Akopian David D See Stephanie K SK Thomä Nicolas H NH Rapé Michael M

Cell 20230720 16

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. ...[more]

PMID: 37478862

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