Property Summary

NCBI Gene PubMed Count 40
PubMed Score 187.06
PubTator Score 61.28

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (5)

Disease log2 FC p
osteosarcoma 1.044 7.4e-03
medulloblastoma, large-cell -1.100 3.3e-04
non-small cell lung cancer -1.353 1.4e-27
lung adenocarcinoma -1.400 1.8e-15
ovarian cancer -1.800 1.2e-07

 GWAS Trait (1)

Protein-protein Interaction (2)

Gene RIF (28)

PMID Text
26990986 GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome.
26188093 Although abnormal CRBN function may be associated with intellectual disability disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection.
26119939 The anti-PEL effects of IMiDs involved cereblon-dependent suppression of IRF4 and rapid degradation of IKZF1, but not IKZF3. Small hairpin RNA-mediated knockdown of MYC enhanced the cytotoxicity of IMiDs
26024445 Structural dynamics of the cereblon ligand binding domain.
26021757 Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels.
25858704 A copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability.
25569776 Studied the protein cereblon , which has been recently indentified as a primary target of thalidomide and its C-terminal part as responsible for binding thalidomide within a domain carrying several invariant cysteine and tryptophan residues.
25284710 High levels of full-length CRBN mRNA in lower risk 5q deletion patients are necessary for the efficacy of lenalidomide.
25108355 The study presents the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide.
25043012 structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide
24925210 Data suggest that cereblon (CRBN) expression in peripheral blood chronic lymphocytic leukemia (CLL) cells is independent of prognostic factors and may be considered a potential biomarker.
24687382 CRBN expression in bone marrow myeloma cells is associated with superior treatment response to lenalidomide in refractory myeloma and thalidomide/dexamethasone in new patients. CRBN is a crucial factor for the anti-MM effect of immunomodulators.
24328678 Presents a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4(CRBN) , leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
24166296 In the three intrinsically IMiD-resistant cell lines that clearly express detectable levels of cereblon, the absence of CRBN and DDB1 mutations suggest that potential cereblon-independent mechanisms of resistance exist
24129344 Data indicate that low cereblon (CRBN) expression can predict resistance to immunomodulatory drug (IMiD monotherapy and is a predictive biomarker for survival outcomes.
24118365 CRBN expression may provide a biomarker to predict response to Immunomodulatory drugs in patients with MM and its high expression can serve as a marker of good prognosis.
23992230 CRBN and IRF4 have been shown to be associated with response to lenalidomide in patients, these findings do not translate back to HMCLs, which could be attributable to factors present in the bone marrow microenvironment.
23983124 Findings suggest an approach for the treatment of mental retardation associated with cereblon nonsense mutation.
23434730 We investigated the role of CRBN in response to lenalidomide in myelodysplastic syndrome infants without chromosome 5 deletion.
23233657 We conclude that CRBN expression may be associated with the clinical efficacy of thalidomide.
23026050 These findings suggest that CRBN may modulate proteasome activity by directly interacting with the beta7 subunit.
22698399 Data show that in a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNbeta production.
21860026 CRBN is an essential requirement for immunoregulatory drugs activity and a possible biomarker for the clinical assessment of antimyeloma efficacy.
21232561 CRBN directly interacts with the alpha1 subunit of AMP-activated protein kinase (AMPK alpha1) and inhibits the activation of AMPK activation.
20131966 The results suggest that mutCRBN may cause ARNSID by disrupting the developmental regulation of BK(Ca) in brain regions that are critical for memory and learning.
18414909 Nonsense mutation (R419X) CRBN disturbs the development of adult brain BK(Ca) isoforms. These changes are predicted to result in BK(Ca) channels with a higher intracellular Ca(2+) sensitivity, faster activation, and slower deactivation kinetics.
17380424 This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm.
15557513 A nonsense mutation causing a premature stop codon in CRBN was found in a large kindred with mild mental retardation. ATP-dependent degradation of proteins may play a role in memory and learning.

AA Sequence

MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGR      1 - 70
TLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAE     71 - 140
IYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPS    141 - 210
KPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDF    211 - 280
SYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYV    281 - 350
NPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRS    351 - 420
ALLPTIPDTEDEISPDKVILCL                                                    421 - 442
//

Text Mined References (43)

PMID Year Title
26990986 2016 Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon.
26188093 2015 Cereblon is recruited to aggresome and shows cytoprotective effect against ubiquitin-proteasome system dysfunction.
26119939 2016 Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors.
26024445 2015 Structural dynamics of the cereblon ligand binding domain.
26021757 2015 The Cullin 4A/B-DDB1-Cereblon E3 Ubiquitin Ligase Complex Mediates the Degradation of CLC-1 Chloride Channels.
25858704 2015 Microduplications of 3p26.3p26.2 containing CRBN gene in patients with intellectual disability and behavior abnormalities.
25569776 2015 The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the ?-tent fold.
25416956 2014 A proteome-scale map of the human interactome network.
25284710 2015 High level of full-length cereblon mRNA in lower risk myelodysplastic syndrome with isolated 5q deletion is implicated in the efficacy of lenalidomide.
25108355 2014 Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs.
25043012 2014 Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide.
24925210 2015 Cereblon expression predicts clinical response in chronic lymphocytic leukemia treated with a thalidomide/fludarabine regimen.
24687382 2014 Expression of cereblon protein assessed by immunohistochemicalstaining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, but not bortezomib-based treatment, in patients with multiple myeloma.
24529757 2014 Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
24328678 2014 Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.).
24166296 2014 Absence of mutations in cereblon (CRBN) and DNA damage-binding protein 1 (DDB1) genes and significance for IMiD therapy.
24129344 2014 The clinical significance of cereblon expression in multiple myeloma.
24118365 2014 Do baseline Cereblon gene expression and IL-6 receptor expression determine the response to thalidomide-dexamethasone treatment in multiple myeloma patients?
23992230 2013 Responsiveness of cytogenetically discrete human myeloma cell lines to lenalidomide: lack of correlation with cereblon and interferon regulatory factor 4 expression levels.
23983124 2013 A mental retardation-linked nonsense mutation in cereblon is rescued by proteasome inhibition.
23434730 2013 A G polymorphism in the CRBN gene acts as a biomarker of response to treatment with lenalidomide in low/int-1 risk MDS without del(5q).
23233657 2013 High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance.
23218918 2013 White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23026050 2012 Cereblon inhibits proteasome activity by binding to the 20S core proteasome subunit beta type 4.
22698399 2012 Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma.
22542470 2012 Genome-wide association study of antibody response to smallpox vaccine.
21860026 2011 Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide.
21232561 2011 Functional modulation of AMP-activated protein kinase by cereblon.
20223979 2010 Identification of a primary target of thalidomide teratogenicity.
20131966 2010 Temporal and spatial mouse brain expression of cereblon, an ionic channel regulator involved in human intelligence.
18414909 2008 Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17380424 2008 Primary function analysis of human mental retardation related gene CRBN.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16641997 2006 The DNA sequence, annotation and analysis of human chromosome 3.
15557513 2004 A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
10932263 2000 A gene for nonsyndromic mental retardation maps to chromosome 3p25-pter.
10931946 2000 Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.