ArticleCell research2018
Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 129 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- USP15 mutation associated with autism spectrum disorder alters progenitor fate and neuronal maturation in human brain organoids.Molecules and cells · 2026Article
- Novel Mutations in the MC2R Gene in a Patient With Familial Glucocorticoid Deficiency (FGD): A Case Report and Functional Study.Molecular genetics & genomic medicine · 2026Article
- Anti-asthma drug montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling.Signal transduction and targeted therapy · 2026Article
- MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes.Nature communications · 2026Article
- RNF126 writes a non-canonical ubiquitin code on midnolin to tune protein stability.Acta biochimica et biophysica Sinica · 2026Article
- Liquid-liquid phase separation couples MKRN2-mediated ubiquitination of CSDE1 with neurodevelopmental disorders.Frontiers in cellular neuroscience · 2026Article
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- The functional study of novel KLHL3 missense mutations associated with pseudohypoaldosteronism type II.Endocrine · 2025Article
- Restoring Retinoic Acid: Alleviating Autism-Like Behaviors in Sox5-Deficient Mice.Neuroscience bulletin · 2025Article
- Cingulate retinoic acid signaling regulates neuropathic pain and comorbid anxiodepression via extracellular matrix homeostasis.The Journal of clinical investigation · 2025Article
- Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving.Molecular psychiatry · 2025Article
- TRIM25 ubiquitinates and degrades p62/SQSTM1 to suppress autophagy.Acta biochimica et biophysica Sinica · 2025Article
- Integrated quantitative proteomics and phosphoproteomics analysis reveals USP46-POU4F1-HPSE signaling axis in the pathogenesis of Hirschsprung disease.Acta biochimica et biophysica Sinica · 2025Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- Prenatal Exposure to Azadiradione Leads to Developmental Disabilities.Molecular neurobiology · 2025Article
- NEAT1 Promotes Valproic Acid-Induced Autism Spectrum Disorder by Recruiting YY1 to Regulate UBE3A Transcription.Molecular neurobiology · 2025Article
- NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice.Frontiers in neuroscience · 2025Article
- A TRIM21-based method for targeted protein degradation.Acta biochimica et biophysica Sinica · 2024Article
- Autism Spectrum Disorder Pathogenesis-A Cross-Sectional Literature Review Emphasizing Molecular Aspects.International journal of molecular sciences · 2024Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The autism spectrum disorders (ASDs) are a collection of human neurological disorders with heterogeneous etiologies. Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner. Excessive UBE3A dosage was found to impair RA-mediated neuronal homeostatic synaptic plasticity. ASD-like symptoms were recapitulated in mice by overexpressing UBE3A in the prefrontal cortex or by administration of an ALDH1A antagonist, whereas RA supplements significantly alleviated excessive UBE3A dosage-induced ASD-like phenotypes. By identifying reduced RA signaling as an underlying mechanism in ASD phenotypes linked to UBE3A hyperactivities, our findings introduce a new vista of ASD etiology and facilitate a mode of therapeutic development against this increasingly prevalent disease.
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