ArticlePLoS genetics2018
CRL4 antagonizes SCFFbxo7-mediated turnover of cereblon and BK channel to regulate learning and memory.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Fibronectin1-Expressing Subicular Circuits Selectively Govern the Retrieval of Novel Object Recognition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cereblon-related mild intellectual disability disrupts response inhibition and uniformity of group-individual strategies.Frontiers in neuroscience · 2026Article
- Paraoxonase 3 regulates the pore-forming α subunit of the large-conductance KBiochimica et biophysica acta. Molecular cell research · 2025Article
- Resolving transitions between distinct phases of memory consolidation at high resolution iniScience · 2024Article
- Enhanced homeostatic sleep response and decreased neurodegenerative proteins in cereblon knock-out mice.Communications biology · 2024Article
- Ubiquitin-specific proximity labeling for the identification of E3 ligase substrates.Nature chemical biology · 2024Article
- Cullin-RING E3 ubiquitin ligase 4 regulates neurite morphogenesis during neurodevelopment.iScience · 2024Article
- Human Herpesvirus 6A U4 Inhibits Proteasomal Degradation of the Amyloid Precursor Protein.Journal of virology · 2022Article
- Effect of an autism-associatedCurrent research in physiology · 2022Article
- An emerging spectrum of variants and clinical features inChannels (Austin, Tex.) · 2021Review
- Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy.Journal of personalized medicine · 2021Review
- Immunomodulatory effect of NEDD8-activating enzyme inhibition in Multiple Myeloma: upregulation of NKG2D ligands and sensitization to Natural Killer cell recognition.Cell death & disease · 2021Article
- Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them.International journal of molecular sciences · 2021Review
- Coronary Large Conductance CaFrontiers in physiology · 2021Review
- Regulation of KCNMA1 transcription by Nrf2 in coronary arterial smooth muscle cells.Journal of molecular and cellular cardiology · 2020Article
- Caspase-8 Inhibition Prevents the Cleavage and Degradation of E3 Ligase Substrate Receptor Cereblon and Potentiates Its Biological Function.Frontiers in cell and developmental biology · 2020Article
- The absence of NIPA2 enhances neural excitability through BK (big potassium) channels.CNS neuroscience & therapeutics · 2019Article
- Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity.The Journal of cell biology · 2019Article
- Cereblon attenuates DNA damage-induced apoptosis by regulating the transcription-independent function of p53.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intellectual disability (ID), one of the most common human developmental disorders, can be caused by genetic mutations in Cullin 4B (Cul4B) and cereblon (CRBN). CRBN is a substrate receptor for the Cul4A/B-DDB1 ubiquitin ligase (CRL4) and can target voltage- and calcium-activated BK channel for ER retention. Here we report that ID-associated CRL4CRBN mutations abolish the interaction of the BK channel with CRL4, and redirect the BK channel to the SCFFbxo7 ubiquitin ligase for proteasomal degradation. Glioma cell lines harbouring CRBN mutations record density-dependent decrease of BK currents, which can be restored by blocking Cullin ubiquitin ligase activity. Importantly, mice with neuron-specific deletion of DDB1 or CRBN express reduced BK protein levels in the brain, and exhibit similar impairment in learning and memory, a deficit that can be partially rescued by activating the BK channel. Our results reveal a competitive targeting of the BK channel by two ubiquitin ligases to achieve exquisite control of its stability, and support changes in neuronal excitability as a common pathogenic mechanism underlying CRL4CRBN-associated ID.
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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.