Gene Symbol: CELF2
Description: CUGBP Elav-like family member 2
Alias: BRUNOL3, CELF-2, CUG-BP2, CUGBP2, ETR-3, ETR3, NAPOR, CUGBP Elav-like family member 2, CUG triplet repeat RNA-binding protein 2, CUG-BP- and ETR-3-like factor 2, ELAV-type RNA-binding protein 3, KDM2B/CELF2 fusion, RNA-binding protein BRUNOL-3, bruno-like protein 3, neuroblastoma apoptosis-related RNA-binding protein
Species: human
Products:     CELF2

Top Publications

  1. Ladd A, Charlet N, Cooper T. The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing. Mol Cell Biol. 2001;21:1285-96 pubmed
    ..We propose that ETR-3 is a major regulator of cTNT alternative splicing and that the CELF family plays an important regulatory role in cell-specific alternative splicing during normal development and disease. ..
  2. Singh G, Charlet B N, Han J, Cooper T. ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in vivo. Nucleic Acids Res. 2004;32:1232-41 pubmed
    ..These results identify specific regions of ETR-3 and CELF4 that are likely targets of protein-protein interactions required for splicing activation. ..
  3. Good P, Chen Q, Warner S, Herring D. A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator. J Biol Chem. 2000;275:28583-92 pubmed
    ..The human BRUNOL2 and BRUNOL3 are 92% identical in the RNA-binding domains, although the BRUNOL2 gene is expressed ubiquitously whereas BRUNOL3 ..
  4. Walker M, Brown S, Riehl T, Stenson W, Stappenbeck T. Growth factor regulation of prostaglandin-endoperoxide synthase 2 (Ptgs2) expression in colonic mesenchymal stem cells. J Biol Chem. 2010;285:5026-39 pubmed publisher
    ..This stabilization was mediated partially through a mechanism involving endogenous CUG-binding protein 2 (CUGbp2)...
  5. Wang X, Sun C, Quiñones Lombraña A, Singh P, Landier W, Hageman L, et al. CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children's Oncology Group Genome-Wide Association Study. J Clin Oncol. 2016;34:863-70 pubmed publisher
  6. Del Pino Sans J, Krishnan S, Aggison L, Adams H, Shrikant M, López Giráldez F, et al. Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol. Neuroscience. 2015;303:312-22 pubmed publisher
    ..changed similarly in males and E2-treated females, the gene encoding CUG triplet repeat, RNA-binding protein 2 (Cugbp2), a proapoptotic protein, showed the highest fold-changes...
  7. Suyal S, Singh M, Shekhar H, Srivastava S. In silico screening of proteins targeting circulating miRNAs for improved diagnosis of multiple myeloma. Biochem Biophys Res Commun. 2018;497:577-582 pubmed publisher
    ..Five RNA binding proteins TROVE2, CUGBP2, DHX8, PUM2 and DKC1 were used for molecular docking studies...
  8. Gu L, Wang H, Wang J, Guo Y, Tang Y, Mao Y, et al. Reconstitution of HuR-Inhibited CUGBP1 Expression Protects Cardiomyocytes from Acute Myocardial Infarction-Induced Injury. Antioxid Redox Signal. 2017;27:1013-1026 pubmed publisher
    ..The reconstitution of CUGBP1 could be developed as a potential therapeutic option for the management of MI. Antioxid. Redox Signal. 27, 1013-1026. ..
  9. Del Pino Sans J, Clements K, Suvorov A, Krishnan S, Adams H, Petersen S. Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin may alter LH release patterns by abolishing sex differences in GABA/glutamate cell number and modifying the transcriptome of the male anteroventral periventricular nucleus. Neuroscience. 2016;329:239-53 pubmed publisher
    ..CUG triplet repeat, RNA binding protein 2 (cugbp2) is particularly interesting because it is sex-specific, oppositely regulated by estradiol (E2) and TCDD...

More Information


  1. Okuda J, Takeuchi Y, Yasuda M, Nakai T. ORF13 in the Type III secretion system gene cluster of Edwardsiella tarda binds to the mammalian factor Cugbp2. Dis Aquat Organ. 2016;119:173-7 pubmed publisher
    ..Then, using a yeast 2-hybrid screen, we show that the mammalian factor Cugbp2, which regulates apoptosis in breast cancer cells, directly interacts with ORF13...
  2. Lu X, Timchenko N, Timchenko L. Cardiac elav-type RNA-binding protein (ETR-3) binds to RNA CUG repeats expanded in myotonic dystrophy. Hum Mol Genet. 1999;8:53-60 pubmed
    ..Our results suggest the existence of a family of proteins that bind to CUG repeats and might be affected in DM by expansion of CUG repeats. ..
  3. Mukhopadhyay D, Houchen C, Kennedy S, Dieckgraefe B, Anant S. Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2. Mol Cell. 2003;11:113-26 pubmed
    ..b>CUGBP2, a predominantly nuclear protein, is also rapidly induced in response to radiation and translocates to the ..
  4. Jakstaite A, Maziukiene A, Silkuniene G, Kmieliute K, Dauksa A, Paskauskas S, et al. Upregulation of cugbp2 increases response of pancreatic cancer cells to chemotherapy. Langenbecks Arch Surg. 2016;401:99-111 pubmed publisher
    Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic ..
  5. Fan B, Jiao B, Fan F, Lu S, Song J, Guo C, et al. Downregulation of miR-95-3p inhibits proliferation, and invasion promoting apoptosis of glioma cells by targeting CELF2. Int J Oncol. 2015;47:1025-33 pubmed publisher
    ..Luciferase reporter was employed to confirm the binding sites in 3'UTR region of CELF2 for miR‑95‑3p...
  6. Hwang D, Hwang W, Liew C. Single pass sequencing of a unidirectional human fetal heart cDNA library to discover novel genes of the cardiovascular system. J Mol Cell Cardiol. 1994;26:1329-33 pubmed
    ..L.F. Sequencer. Partial cDNA sequences, or expressed sequence tags (ESTs) were searched against the Genbank and EMBL databases to identify novel genes expressed in the human cardiovascular system. ..
  7. Anant S, Henderson J, Mukhopadhyay D, Navaratnam N, Kennedy S, Min J, et al. Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor. J Biol Chem. 2001;276:47338-51 pubmed
    ..We have now identified CUGBP2, a 54-kDa RNA-binding protein, as a component of this holoenzyme...
  8. Ajith S, Gazzara M, Cole B, Shankarling G, Martinez N, Mallory M, et al. Position-dependent activity of CELF2 in the regulation of splicing and implications for signal-responsive regulation in T cells. RNA Biol. 2016;13:569-81 pubmed publisher
    b>CELF2 is an RNA binding protein that has been implicated in developmental and signal-dependent splicing in the heart, brain and T cells...
  9. Mallory M, Allon S, Qiu J, Gazzara M, Tapescu I, Martinez N, et al. Induced transcription and stability of CELF2 mRNA drives widespread alternative splicing during T-cell signaling. Proc Natl Acad Sci U S A. 2015;112:E2139-48 pubmed publisher
    ..Here we demonstrate that expression of the splicing factor CELF2 (CUGBP, Elav-like family member 2) is regulated in response to T-cell signaling through combined increases in ..
  10. Natarajan G, Ramalingam S, Ramachandran I, May R, Queimado L, Houchen C, et al. CUGBP2 downregulation by prostaglandin E2 protects colon cancer cells from radiation-induced mitotic catastrophe. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1235-44 pubmed publisher
    ..Exposure of colon cancer cells to IR leads to increased CUGBP2 expression...
  11. Diarra Dit Konté N, Krepl M, Damberger F, Ripin N, Duss O, Sponer J, et al. Aromatic side-chain conformational switch on the surface of the RNA Recognition Motif enables RNA discrimination. Nat Commun. 2017;8:654 pubmed publisher
  12. Mukhopadhyay D, Jung J, Murmu N, Houchen C, Dieckgraefe B, Anant S. CUGBP2 plays a critical role in apoptosis of breast cancer cells in response to genotoxic injury. Ann N Y Acad Sci. 2003;1010:504-9 pubmed
    ..We have previously demonstrated that RNA binding protein CUGBP2 binds AU-rich sequences to regulate COX-2 mRNA translation...
  13. Ramalingam S, Natarajan G, Schafer C, Subramaniam D, May R, Ramachandran I, et al. Novel intestinal splice variants of RNA-binding protein CUGBP2: isoform-specific effects on mitotic catastrophe. Am J Physiol Gastrointest Liver Physiol. 2008;294:G971-81 pubmed publisher
    CUG triplet repeat-binding protein 2 (CUGBP2) is a RNA-binding protein that regulates mRNA translation and modulates apoptosis...
  14. Guo Y, Sun M, Li J, Liu T, Huang H, Chen J, et al. Association of CELF2 polymorphism and the prognosis of nasopharyngeal carcinoma in southern Chinese population. Oncotarget. 2015;6:27176-86 pubmed publisher
    ..Combined analysis revealed that SNP rs3740194 in CELF2 was significantly associated with the decreased risk of death with a Hazard ratio (HR) of 0...
  15. Martinez N, Agosto L, Qiu J, Mallory M, Gazzara M, Barash Y, et al. Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation. Genes Dev. 2015;29:2054-66 pubmed publisher
    ..2 is dependent on the presence of flanking sequences and the JNK-induced expression of the RNA-binding protein CELF2, which binds to these regulatory elements...
  16. Murmu N, Jung J, Mukhopadhyay D, Houchen C, Riehl T, Stenson W, et al. Dynamic antagonism between RNA-binding protein CUGBP2 and cyclooxygenase-2-mediated prostaglandin E2 in radiation damage. Proc Natl Acad Sci U S A. 2004;101:13873-8 pubmed
    ..In previous studies, we demonstrated that the RNA-binding protein CUGBP2 regulates the stability and translation of COX-2 mRNA by interacting with AU-rich sequences in 3' UTR...
  17. Schultz A, Preussner M, Bunse M, Karni R, Heyd F. Activation-Dependent TRAF3 Exon 8 Alternative Splicing Is Controlled by CELF2 and hnRNP C Binding to an Upstream Intronic Element. Mol Cell Biol. 2017;37: pubmed publisher
    ..A small interfering RNA screen, followed by cross-link immunoprecipitation and mutational analyses, identified CELF2 and hnRNP C as trans-acting factors that directly bind the regulatory sequence and together mediate ..
  18. Do C, Lang C, Lin J, Darbary H, Krupska I, Gaba A, et al. Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation. Am J Hum Genet. 2016;98:934-955 pubmed publisher
    ..CD69, FRMD1, IRF1, KBTBD11, and S100A(?)-ILF2, associated with immune phenotypes, MYT1L, PTPRN2, CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders,..
  19. Sureban S, Murmu N, Rodriguez P, May R, Maheshwari R, Dieckgraefe B, et al. Functional antagonism between RNA binding proteins HuR and CUGBP2 determines the fate of COX-2 mRNA translation. Gastroenterology. 2007;132:1055-65 pubmed
    ..Although structurally homologous RNA binding proteins HuR and CUGBP2 stabilize COX-2 mRNA, HuR induces whereas CUGBP2 inhibits COX-2 mRNA translation...
  20. Yang P, Xu M, Liu Z, Tao Q, Lu S, Li H, et al. Genetic association of CUGBP2 and DNMBP with Alzheimer' s disease in the Chinese Han population. Curr Alzheimer Res. 2015;12:228-32 pubmed
    Recently, candidate genetic studies revealed the single nucleotide polymorphisms (SNPs) of CUGBP2 (rs2242451) and DNMBP (rs11190305 and rs3740058) associated with Alzheimer's disease (AD)...
  21. Park T, Hwang J, Go M, Lee H, Jang H, Choi Y, et al. Genome-wide association study of liver enzymes in korean children. Genomics Inform. 2013;11:149-54 pubmed publisher
    ..are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.
  22. Subramaniam D, Natarajan G, Ramalingam S, Ramachandran I, May R, Queimado L, et al. Translation inhibition during cell cycle arrest and apoptosis: Mcl-1 is a novel target for RNA binding protein CUGBP2. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1025-32 pubmed publisher
    b>CUGBP2, a translation inhibitor, induces colon cancer cells to undergo apoptosis. Mcl-1, an antiapoptotic Bcl-2 family protein, interferes with mitochondrial activation to inhibit apoptosis...
  23. Li D, Bachinski L, Roberts R. Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia. Genomics. 2001;74:396-401 pubmed
    Neuroblastoma apoptosis-related RNA-binding protein (NAPOR; HGMW-approved symbol CUGBP2) is a newly discovered gene prominently induced during apoptosis, suggesting that it plays a role during apoptosis...
  24. Lichtner P, Attie Bitach T, Schuffenhauer S, Henwood J, Bouvagnet P, Scambler P, et al. Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p. J Mol Med (Berl). 2002;80:431-42 pubmed
    ..The genomic draft sequence of this region contains only one known gene, BRUNOL3 ( NAPOR, CUGBP2, ETR3)...
  25. Chen Z, Eggerman T, Patterson A. ApoB mRNA editing is mediated by a coordinated modulation of multiple apoB mRNA editing enzyme components. Am J Physiol Gastrointest Liver Physiol. 2007;292:G53-65 pubmed
    ..apoB mRNA editing from approximately 3% to 88% begins with decreased levels of inhibitory CUG binding protein 2 (CUGBP2) expression followed by increased levels of apoB mRNA editing enzyme (apobec)-1 and apobec-1 complementation ..
  26. Mallory M, Jackson J, Weber B, Chi A, Heyd F, Lynch K. Signal- and development-dependent alternative splicing of LEF1 in T cells is controlled by CELF2. Mol Cell Biol. 2011;31:2184-95 pubmed publisher
    ..inclusion of exon 6 is dependent on the signal-induced increase in expression and binding of the splicing factor CELF2 to two intronic sequences flanking the regulated exon...
  27. Choi D, Ito T, Tsukahara F, Hirai M, Sakaki Y. Developmentally-regulated expression of mNapor encoding an apoptosis-induced ELAV-type RNA binding protein. Gene. 1999;237:135-42 pubmed
    ..The neuroblastoma apoptosis-related RNA binding protein (NAPOR) is an ELAV-type RNA-binding protein with three characteristic RNP2/RNP1-type RRMs, which we identified as a gene ..
  28. Dhaenens C, Tran H, Frandemiche M, Carpentier C, Schraen Maschke S, Sistiaga A, et al. Mis-splicing of Tau exon 10 in myotonic dystrophy type 1 is reproduced by overexpression of CELF2 but not by MBNL1 silencing. Biochim Biophys Acta. 2011;1812:732-42 pubmed publisher
    ..splicing factors muscleblind-like 1 (MBNL1), CUGBP1 and ETR3-like factor 1 (CELF1), CUGBP1 and ETR3-like factor 2 (CELF2), and CUGBP1 and ETR3-like factor 4 (CELF4) or a dominant-negative CUGBP1 and ETR-3 like factor (CELF) factor on ..
  29. Wijsman E, Pankratz N, Choi Y, Rothstein J, Faber K, Cheng R, et al. Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE. PLoS Genet. 2011;7:e1001308 pubmed publisher
    ..Analyses that stratified on APOE genotypes identified SNPs on chromosome 10p14 in CUGBP2 with genome-wide significant evidence for association within APOE ?4 homozygotes (e.g., rs201119, p?=?1.5×10(-8))...
  30. Han J, Cooper T. Identification of CELF splicing activation and repression domains in vivo. Nucleic Acids Res. 2005;33:2769-80 pubmed
    ..This analysis was performed in parallel on two CELF proteins, ETR-3 (CUG-BP2, NAPOR, BRUNOL3) and CELF4 (BRUNOL4)...