ArticleOncotarget2016
The HERC2 ubiquitin ligase is essential for embryonic development and regulates motor coordination.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Proteasome dysfunction underlies HERC2-linked neurodevelopmental disorder with Angelman-like clinical features.Cell death discovery · 2026Article
- TRIM7-mediated autophagy-lysosomal signaling is essential for preimplantation development in mice.Journal of translational medicine · 2026Article
- Whole-Exome Sequencing Identifies Novel Genetic Variants Associated with Unexplained Neurodevelopmental Disorders in Children.International journal of molecular sciences · 2026Article
- Duration of contact sports play associated with aberrant DNA methylation in human frontal cortex.Research square · 2026Article
- Distinct Proteomic Brain States Underlying Long-Term Memory Formation in Aversive Operant Conditioning.Journal of proteome research · 2025Article
- Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder.Cell death discovery · 2024Article
- Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling.Cell reports · 2023Article
- Article
- ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain.Nature neuroscience · 2023Article
- The genomic landscape of familial glioma.Science advances · 2023Article
- Stem cell models of Angelman syndrome.Frontiers in cell and developmental biology · 2023Review
- Whole-genome sequencing analysis in families with recurrent pregnancy loss: A pilot study.PloS one · 2023Article
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- Novel loss-of-function mutation inJournal of medical genetics · 2021Article
- Article
- Exome sequencing study of partial agenesis of the corpus callosum in men with developmental delay, epilepsy, and microcephaly.Molecular genetics & genomic medicine · 2020Article
- HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory.Frontiers in neuroanatomy · 2020Article
- Regulation of the MDM2-p53 pathway by the ubiquitin ligase HERC2.Molecular oncology · 2020Article
- Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis.Acta neuropathologica communications · 2019Article
- HERCing: Structural and Functional Relevance of the Large HERC Ubiquitin Ligases.Frontiers in physiology · 2019Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 4 countries.
Funding
Abstract
A mutation in the HERC2 gene has been linked to a severe neurodevelopmental disorder with similarities to the Angelman syndrome. This gene codifies a protein with ubiquitin ligase activity that regulates the activity of tumor protein p53 and is involved in important cellular processes such as DNA repair, cell cycle, cancer, and iron metabolism. Despite the critical role of HERC2 in these physiological and pathological processes, little is known about its relevance in vivo. Here, we described a mouse with targeted inactivation of the Herc2 gene. Homozygous mice were not viable. Distinct from other ubiquitin ligases that interact with p53, such as MDM2 or MDM4, p53 depletion did not rescue the lethality of homozygous mice. The HERC2 protein levels were reduced by approximately one-half in heterozygous mice. Consequently, HERC2 activities, including ubiquitin ligase and stimulation of p53 activity, were lower in heterozygous mice. A decrease in HERC2 activities was also observed in human skin fibroblasts from individuals with an Angelman-like syndrome that express an unstable mutant protein of HERC2. Behavioural analysis of heterozygous mice identified an impaired motor synchronization with normal neuromuscular function. This effect was not observed in p53 knockout mice, indicating that a mechanism independent of p53 activity is involved. Morphological analysis showed the presence of HERC2 in Purkinje cells and a specific loss of these neurons in the cerebella of heterozygous mice. In these animals, an increase of autophagosomes and lysosomes was observed. Our findings establish a crucial role of HERC2 in embryonic development and motor coordination.
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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.