ArticleCell reports2019
Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Focal DEPDC5 loss without disruption to cerebral cortical neuron migration recapitulates DEPDC5-related focal epilepsy.JCI insight · 2025Article
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- The Unified Theory of Neurodegeneration Pathogenesis Based on Axon Deamidation.International journal of molecular sciences · 2025Review
- The Fundamental Neurobiological Mechanism of Oxidative Stress-Related 4E-BP2 Protein Deamidation.International journal of molecular sciences · 2024Article
- Early metformin treatment: An effective approach for targeting fragile X syndrome pathophysiology.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Control of Selective mRNA Translation in Neuronal Subcellular Compartments in Health and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Phytocannabinoids Reduce Inflammation of Primed Macrophages and Enteric Glial Cells: An In Vitro Study.International journal of molecular sciences · 2023Article
- Mnk1/2 kinases regulate memory and autism-related behaviours via Syngap1.Brain : a journal of neurology · 2023Article
- Structure and function of African swine fever virus proteins: Current understanding.Frontiers in microbiology · 2023Review
- TRIP6 regulates the proliferation, migration, invasion and apoptosis of osteosarcoma cells by activating the NF-κB signaling pathway.Experimental and therapeutic medicine · 2020Article
- African Swine Fever Virus Ubiquitin-Conjugating Enzyme Interacts With Host Translation Machinery to Regulate the Host Protein Synthesis.Frontiers in microbiology · 2020Article
- Dysregulating mTORC1-4E-BP2 signaling in GABAergic interneurons impairs hippocampus-dependent learning and memory.Learning & memory (Cold Spring Harbor, N.Y.)Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that 4E-BP2 deamidation is neuron specific, occurs in the human brain, and changes 4E-BP2 subcellular localization, but not its disordered structure state. We demonstrate that deamidated 4E-BP2 is ubiquitinated more and degrades faster than the unmodified protein. We find that enhanced deamidated 4E-BP2 degradation is dependent on Raptor binding, concomitant with increased association with a Raptor-CUL4B E3 ubiquitin ligase complex. Deamidated 4E-BP2 stability is promoted by inhibiting mTORC1 or glutamate receptors. We further demonstrate that deamidated 4E-BP2 regulates the translation of a distinct pool of mRNAs linked to cerebral development, mitochondria, and NF-κB activity, and thus may be crucial for postnatal brain development in neurodevelopmental disorders, such as ASD.
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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.