ArticleeLife2017
A conformational switch regulates the ubiquitin ligase HUWE1.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Structure and mechanism of the HECT ligase HECTD3.Nature communications · 2026Article
- Cryo-EM structure of the human COP1-DET1 ubiquitin ligase complex.Nature communications · 2026Article
- Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1.Nature communications · 2025Article
- Article
- Sphingosine kinase 2 regulates protein ubiquitination networks in neurons.Molecular and cellular neurosciences · 2024Article
- Ubiquitination Insight from Spinal Muscular Atrophy-From Pathogenesis to Therapy: A Muscle Perspective.International journal of molecular sciences · 2024Review
- Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.Nature structural & molecular biology · 2024Article
- Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).Experimental and therapeutic medicine · 2024Review
- Bacterial ligases reveal fundamental principles of polyubiquitin specificity.Molecular cell · 2023Article
- A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.Oncogene · 2023Article
- Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.The EMBO journal · 2023Article
- Bacterial mimicry of eukaryotic HECT ubiquitin ligation.bioRxiv : the preprint server for biology · 2023Article
- Structure of the human UBR5 E3 ubiquitin ligase.Structure (London, England : 1993) · 2023Article
- The ubiquitin-like modifier FAT10 covalently modifies HUWE1 and strengthens the interaction of AMBRA1 and HUWE1.PloS one · 2023Article
- Redefining the catalytic HECT domain boundaries for the HECT E3 ubiquitin ligase family.Bioscience reports · 2022Article
- The HECT family of E3 ubiquitin ligases and PTEN.Seminars in cancer biology · 2022Review
- HECT ubiquitin ligases as accessory proteins of the plant proteasome.Essays in biochemistry · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues-a mechanism that may be exploited for cancer therapy.
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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.