ArticleThe Journal of biological chemistry2013
A mental retardation-linked nonsense mutation in cereblon is rescued by proteasome inhibition.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- The histone demethylase KDM5C enhances the sensitivity of acute myeloid leukemia cells to lenalidomide by stabilizing cereblon.Cellular & molecular biology letters · 2025Article
- E3 ubiquitin ligase UBR5 modulates circadian rhythm by facilitating the ubiquitination and degradation of the key clock transcription factor BMAL1.Acta pharmacologica Sinica · 2024Article
- Lys-63-specific deubiquitinase BRCC36 enhances the sensitivity of multiple myeloma cells to lenalidomide by inhibiting lysosomal degradation of cereblon.Cellular and molecular life sciences : CMLS · 2024Article
- The CBEMBO molecular medicine · 2024Article
- IMiD-Free Interval and IMiDs Sequence: Which Strategy Is Better Suited for Lenalidomide-Refractory Myeloma?Life (Basel, Switzerland) · 2023Review
- PROTAC'ing oncoproteins: targeted protein degradation for cancer therapy.Molecular cancer · 2023Review
- Activity of a Novel Anti-Inflammatory Agent F-3,6'-dithiopomalidomide as a Treatment for Traumatic Brain Injury.Biomedicines · 2022Article
- Finding associations in a heterogeneous setting: statistical test for aberration enrichment.Genome medicine · 2021Article
- Article
- Cereblon Promotes the Ubiquitination and Proteasomal Degradation of Interleukin Enhancer-Binding Factor 2.The protein journal · 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
- Cereblon attenuates DNA damage-induced apoptosis by regulating the transcription-independent function of p53.Cell death & disease · 2019Article
- Ubiquitin-conjugating enzyme UBE2O regulates cellular clock function by promoting the degradation of the transcription factor BMAL1.The Journal of biological chemistry · 2018Article
- Cereblon suppresses the lipopolysaccharide-induced inflammatory response by promoting the ubiquitination and degradation of c-Jun.The Journal of biological chemistry · 2018Article
- The Catalytically Inactive Mutation of the Ubiquitin-Conjugating Enzyme CDC34 Affects its Stability and Cell Proliferation.The protein journal · 2018Article
- Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- CRL4 antagonizes SCFFbxo7-mediated turnover of cereblon and BK channel to regulate learning and memory.PLoS genetics · 2018Article
- A missense mutation in theJournal of medical genetics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
A nonsense mutation in cereblon (CRBN) causes autosomal recessive nonsyndromic mental retardation. Cereblon is a substrate receptor for the Cullin-RING E3 ligase complex and couples the ubiquitin ligase to specific ubiquitination targets. The CRBN nonsense mutation (R419X) results in a protein lacking 24 amino acids at its C terminus. Although this mutation has been linked to mild mental retardation, the mechanism by which the mutation affects CRBN function is unknown. Here, we used biochemical and mass spectrometric approaches to explore the function of this mutant. We show that the protein retains its ability to assemble into a Cullin-RING E3 ligase complex and catalyzes the ubiquitination of CRBN-target proteins. However, we find that this mutant exhibits markedly increased levels of autoubiquitination and is more readily degraded by the proteasome than the wild type protein. We also show that the level of the mutant protein can be restored by a treatment of cells with a clinically utilized proteasome inhibitor, suggesting that this agent may be useful for the treatment of mental retardation associated with the CRBN R419X mutation. These data demonstrate that enhanced autoubiquitination and degradation account for the defect in CRBN activity that leads to mental retardation.
Indexed as
Identifiers
What OpenQuestion holds
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.