ArticleScientific reports2020
Identification of the HECT E3 ligase UBR5 as a regulator of MYC degradation using a CRISPR/Cas9 screen.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Disruption of the SAGA CORE triggers collateral degradation of KAT2A.Nature communications · 2026Article
- Chromatin association promotes UBR5-mediated degradation of Rb.bioRxiv : the preprint server for biology · 2026Article
- Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Systematic identification and characterization of regulators of aryl hydrocarbon receptor signaling.bioRxiv : the preprint server for biology · 2025Article
- A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.Genes & development · 2024Article
- Structural snapshots along K48-linked ubiquitin chain formation by the HECT E3 UBR5.Nature chemical biology · 2024Article
- DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance.Nature communications · 2024Article
- RNF40 epigenetically modulates glycolysis to support the aggressiveness of basal-like breast cancer.Cell death & disease · 2023Article
- DHX9/DNA-tandem repeat-dependent downregulation of ciRNA-Fmn1 in the dorsal horn is required for neuropathic pain.Acta pharmacologica Sinica · 2023Article
- Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.The EMBO journal · 2023Article
- UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability.Molecular cell · 2023Article
- Article
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- UBR5 targets tumor suppressor CDC73 proteolytically to promote aggressive breast cancer.Cell death & disease · 2022Article
- Review
- How Viruses Use the VCP/p97 ATPase Molecular Machine.Viruses · 2021Review
- Ubiquitin-dependent regulation of transcription in development and disease.EMBO reports · 2021Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MYC oncoprotein is a multifunctional transcription factor that regulates the expression of a large number of genes involved in cellular growth, proliferation and metabolism. Altered MYC protein level lead to cellular transformation and tumorigenesis. MYC is deregulated in > 50% of human cancers, rendering it an attractive drug target. However, direct inhibition of this class of proteins using conventional small molecules is challenging due to their intrinsically disordered state. To discover novel posttranslational regulators of MYC protein stability and turnover, we established a genetic screen in mammalian cells by combining a fluorescent protein-based MYC abundance sensor, CRISPR/Cas9-based gene knockouts and next-generation sequencing. Our screen identifies UBR5, an E3 ligase of the HECT-type family, as a novel regulator of MYC degradation. Even in the presence of the well-described and functional MYC ligase, FBXW7, UBR5 depletion leads to accumulation of MYC in cells. We demonstrate interaction of UBR5 with MYC and reduced K48-linked ubiquitination of MYC upon loss of UBR5 in cells. Interestingly, in cancer cell lines with amplified MYC expression, depletion of UBR5 resulted in reduced cell survival, as a consequence of MYC stabilization. Finally, we show that MYC and UBR5 are co-amplified in more than 40% of cancer cells and that MYC copy number amplification correlates with enhanced transcriptional output of UBR5. This suggests that UBR5 acts as a buffer in MYC amplified settings and protects these cells from apoptosis.
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