ArticleScientific reports2017
Impaired oxidative stress response characterizes HUWE1-promoted X-linked intellectual disability.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial.Journal of autism and developmental disorders · 2024Trial
- Tobacco Smoking and Lung Cancer Risk After Negative Baseline Low-Dose Computed Tomography Findings.JAMA network open · 2026Article
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- Novel HUWE1-Related Neurodevelopmental Disorder: Genotypic and Phenotypic Expansion.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2026Article
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Nuclear and Cytoplasmatic Players in Mitochondria-Related CNS Disorders: Chromatin Modifications and Subcellular Trafficking.Biomolecules · 2022Review
- Solenoid architecture of HUWE1 contributes to ligase activity and substrate recognition.Molecular cell · 2021Article
- Increased p53 signaling impairs neural differentiation in HUWE1-promoted intellectual disabilities.Cell reports. Medicine · 2021Article
- O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 modulate seizure susceptibility in C. elegans.PloS one · 2021Article
- The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma.Oncogene · 2020Article
- HECT E3 ubiquitin ligases - emerging insights into their biological roles and disease relevance.Journal of cell science · 2020Review
- The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer.Investigational new drugs · 2020Review
- Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability.Genes · 2020Article
- Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.European journal of medical genetics · 2020Article
- "Two hits - one stone"; increased efficacy of cisplatin-based therapies by targeting PCNA's role in both DNA repair and cellular signaling.Oncotarget · 2018Article
- Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins.Science (New York, N.Y.) · 2018Article
- Additive Effect of Variably Penetrant 22q11.2 Duplication and Pathogenic Mutations in Autism Spectrum Disorder: To Which Extent Does the Tree Hide the Forest?Journal of autism and developmental disorders · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
Abstract
Mutations in the HECT, UBA and WWE domain-containing 1 (HUWE1) E3 ubiquitin ligase cause neurodevelopmental disorder X-linked intellectual disability (XLID). HUWE1 regulates essential processes such as genome integrity maintenance. Alterations in the genome integrity and accumulation of mutations have been tightly associated with the onset of neurodevelopmental disorders. Though HUWE1 mutations are clearly implicated in XLID and HUWE1 regulatory functions well explored, currently much is unknown about the molecular basis of HUWE1-promoted XLID. Here we showed that the HUWE1 expression is altered and mutation frequency increased in three different XLID individual (HUWE1 p.R2981H, p.R4187C and HUWE1 duplication) cell lines. The effect was most prominent in HUWE1 p.R4187C XLID cells and was accompanied with decreased DNA repair capacity and hypersensitivity to oxidative stress. Analysis of HUWE1 substrates revealed XLID-specific down-regulation of oxidative stress response DNA polymerase (Pol) λ caused by hyperactive HUWE1 p.R4187C. The subsequent restoration of Polλ levels counteracted the oxidative hypersensitivity. The observed alterations in the genome integrity maintenance may be particularly relevant in the cortical progenitor zones of human brain, as suggested by HUWE1 immunofluorescence analysis of cerebral organoids. These results provide evidence that impairments of the fundamental cellular processes, like genome integrity maintenance, characterize HUWE1-promoted XLID.
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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.