ArticleThe EMBO journal2023
Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- An Acetylation-Primed SUMOylation Switch Controls RORβ Stability through a p300-SIRT1 Regulatory Axis.Research square · 2026Article
- Acetylation-Primed SUMOylation Drives RORβ Turnover via a p300-SIRT1 Regulatory Axis.bioRxiv : the preprint server for biology · 2026Article
- Systemic degradation of repressive transcription factors gates gene expression and cell fate specification.bioRxiv : the preprint server for biology · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- SMURF2 attenuates NRF2-driven tumor progression by acting as a nuclear brake on NRF2 during cellular stress.Redox biology · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Disruption of the SAGA CORE triggers collateral degradation of KAT2A.Nature communications · 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
- Structure and mechanism of the HECT ligase HECTD3.Nature communications · 2026Article
- A multivalent adaptor mechanism drives the nuclear import of proteasomes.Nature communications · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- MIRAGE: A Bayesian statistical method for gene-level rare-variant analysis incorporating functional annotations.American journal of human genetics · 2026Article
- Nuclear ubiquitination permits Hippo-YAP signal for liver development and tumorigenesis.Nature chemical biology · 2025Article
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation.Nature communications · 2025Article
- Article
- Illuminating ubiquitination mechanisms: How cryo-EM has shed light on Cullin RING E3 ligase function.Current opinion in structural biology · 2025Review
- Revisiting the structure of UBR box from human UBR6.Protein science : a publication of the Protein Society · 2025Article
- Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.Molecular cell · 2025Article
- UBR5 in Tumor Biology: Exploring Mechanisms of Immune Regulation and Possible Therapeutic Implications in MPNST.Cancers · 2025Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin ligase has recently been identified as an important regulator of oncogenes, e.g., MYC, but little is known about its structure or mechanisms of substrate engagement and ubiquitination. Here, we present the cryo-EM structure of human UBR5, revealing an α-solenoid scaffold with numerous protein-protein interacting motifs, assembled into an antiparallel dimer that adopts further oligomeric states. Using cryo-EM processing tools, we observe the dynamic nature of the UBR5 catalytic domain, which we postulate is important for its enzymatic activity. We characterise the proteasomal nuclear import factor AKIRIN2 as an interacting protein and propose UBR5 as an efficient ubiquitin chain elongator. This preference for ubiquitinated substrates and several distinct domains for protein-protein interactions may explain how UBR5 is linked to several different signalling pathways and cancers. Together, our data expand on the limited knowledge of the structure and function of HECT E3 ligases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.