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Series GSE234200 Query DataSets for GSE234200
Status Public on Jun 07, 2023
Title Orphan quality control shapes network dynamics and gene expression
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design To investigate the global effect of UBR5 loss on gene expression, we generated a UBR5 knockout HEK 293T cell line using CRISPR. We then performed comparative gene expression profiling analysis via RNA-seq from both unedited (WT) and ∆UBR5 HEK 293T cells in biological triplicate. We also performed a similar anaylsis in H1 hESCs treated with either non-targeting control siRNAs or siRNAs against UBR5.
Contributor(s) Mark KG, Kolla S, Aguirre JD, Garshott DM, Schmitt S, Haakonsen DL, Xu C, Kater L, Kempf G, Martínez-González B, Akopian D, See SK, Thomä NH, Rapé M
Citation(s) 37478862
Submission date Jun 05, 2023
Last update date Sep 07, 2023
Contact name Michael Rapé
Organization name University of California Berkeley
Department Molecular and Cell Biology
Street address 330F Li Ka Shing Center
City Berkeley
State/province CA
ZIP/Postal code 94720
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (18)
GSM7454050 WT_1_Rep1
GSM7454051 WT_2_Rep1
GSM7454052 WT_3_Rep1
BioProject PRJNA980276

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Supplementary file Size Download File type/resource
GSE234200_293T_gene_fpkm.xls.gz 3.0 Mb (ftp)(http) XLS
GSE234200_293T_gene_fpkm_Rep2.xls.gz 2.9 Mb (ftp)(http) XLS
GSE234200_H1_gene_fpkm.xls.gz 3.4 Mb (ftp)(http) XLS
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