ArticleMolecular cell2021
Solenoid architecture of HUWE1 contributes to ligase activity and substrate recognition.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Fluorophore placement and size impact E2 ubiquitination efficiency.The Biochemical journal · 2026Article
- 35 Individuals With HUWE1-Related Neurodevelopmental Disorder and Suggested Clinical Evaluations.American journal of medical genetics. Part A · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Structure and mechanism of the HECT ligase HECTD3.Nature communications · 2026Article
- Sequence-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.ChemistryEurope · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.bioRxiv : the preprint server for biology · 2025Article
- Enrichment-Free, Targeted Covalent Drug Discovery in Live Cells.ACS chemical biology · 2025Article
- Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1.Nature communications · 2025Article
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- Clinical applications of and molecular insights from RNA sequencing in a rare disease cohort.Genome medicine · 2025Article
- Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Activity-based protein profiling reveals both canonical and novel ubiquitin pathway enzymes in Plasmodium.PLoS pathogens · 2025Article
- Context-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.Journal of the American Chemical Society · 2025Article
- CDK9 recruits HUWE1 to degrade RARα and offers therapeutic opportunities for cutaneous T-cell lymphoma.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
HECT ubiquitin ligases play essential roles in metazoan development and physiology. The HECT ligase HUWE1 is central to the cellular stress response by mediating degradation of key death or survival factors, including Mcl1, p53, DDIT4, and Myc. Although mutations in HUWE1 and related HECT ligases are widely implicated in human disease, our molecular understanding remains limited. Here we present a comprehensive investigation of full-length HUWE1, deepening our understanding of this class of enzymes. The N-terminal ∼3,900 amino acids of HUWE1 are indispensable for proper ligase function, and our cryo-EM structures of HUWE1 offer a complete molecular picture of this large HECT ubiquitin ligase. HUWE1 forms an alpha solenoid-shaped assembly with a central pore decorated with protein interaction modules. Structures of HUWE1 variants linked to neurodevelopmental disorders as well as of HUWE1 bound to a model substrate link the functions of this essential enzyme to its three-dimensional organization.
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Registered trials
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.