Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6JQ5RS)

• DOT Name: CUGBP Elav-like family member 1 (CELF1)
• Synonyms: CELF-1; 50 kDa nuclear polyadenylated RNA-binding protein; Bruno-like protein 2; CUG triplet repeat RNA-binding protein 1; CUG-BP1; CUG-BP- and ETR-3-like factor 1; Deadenylation factor CUG-BP; Embryo deadenylation element-binding protein homolog; EDEN-BP homolog; RNA-binding protein BRUNOL-2
• Gene Name: CELF1
• Related Disease:
  Acute myocardial infarction
  Arrhythmogenic right ventricular cardiomyopathy
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Cardiomyopathy
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Esophageal cancer
  Fatty liver disease
  Gastric cancer
  Glioma
  Hepatitis C virus infection
  Hypertrophic cardiomyopathy
  Laryngeal carcinoma
  Liver cancer
  Lung neoplasm
  Multiple sclerosis
  Muscular dystrophy
  Myocardial infarction
  Myopathy
  Myotonic dystrophy type 1
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obesity
  Oral cancer
  Squamous cell carcinoma
  Stomach cancer
  Alzheimer disease
  Hepatocellular carcinoma
  Lung cancer
  Neurofibromatosis type 1
  Advanced cancer
  Melanoma
  Myotonic dystrophy
  Myotonic dystrophy type 2
  Type-1/2 diabetes
• UniProt ID: CELF1_HUMAN
• PDB ID: 2CPZ; 2DHS; 2RQ4; 2RQC; 3NMR; 3NNA; 3NNC; 3NNH
• Pfam ID: PF00076
• Sequence:
  MNGTLDHPDQPDLDAIKMFVGQVPRTWSEKDLRELFEQYGAVYEINVLRDRSQNPPQSKG
  CCFVTFYTRKAALEAQNALHNMKVLPGMHHPIQMKPADSEKNNAVEDRKLFIGMISKKCT
  ENDIRVMFSSFGQIEECRILRGPDGLSRGCAFVTFTTRAMAQTAIKAMHQAQTMEGCSSP
  MVVKFADTQKDKEQKRMAQQLQQQMQQISAASVWGNLAGLNTLGPQYLALYLQLLQQTAS
  SGNLNTLSSLHPMGGLNAMQLQNLAALAAAASAAQNTPSGTNALTTSSSPLSVLTSSGSS
  PSSSSSNSVNPIASLGALQTLAGATAGLNVGSLAGMAALNGGLGSSGLSNGTGSTMEALT
  QAYSGIQQYAAAALPTLYNQNLLTQQSIGAAGSQKEGPEGANLFIYHLPQEFGDQDLLQM
  FMPFGNVVSAKVFIDKQTNLSKCFGFVSYDNPVSAQAAIQSMNGFQIGMKRLKVQLKRSK
  NDSKPY
• Function: RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Acts both as an activator and as a repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Activates SM exon 5 inclusion by antagonizing the repressive effect of PTB. Promotes exclusion of exon 11 of the INSR pre-mRNA. Inhibits, together with HNRNPH1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Increases translation and controls the choice of translation initiation codon of CEBPB mRNA. Increases mRNA translation of CEBPB in aging liver. Increases translation of CDKN1A mRNA by antagonizing the repressive effect of CALR3. Mediates rapid cytoplasmic mRNA deadenylation. Recruits the deadenylase PARN to the poly(A) tail of EDEN-containing mRNAs to promote their deadenylation. Required for completion of spermatogenesis. Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK and to Bruno response elements (BREs). Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA. Binds to AU-rich sequences (AREs or EDEN-like) localized in the 3'-UTR of JUN and FOS mRNAs. Binds to the IR RNA. Binds to the 5'-region of CDKN1A and CEBPB mRNAs. Binds with the 5'-region of CEBPB mRNA in aging liver. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF2, negatively regulates the processing to mature miRNA.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	Strong	Genetic Variation	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[4]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[5]
Dilated cardiomyopathy	DISX608J	Strong	Altered Expression	[6]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[6]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[3]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[4]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Altered Expression	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[9]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[10]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[11]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[4]
Lung neoplasm	DISVARNB	Strong	Biomarker	[12]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[13]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[14]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[6]
Myopathy	DISOWG27	Strong	Altered Expression	[15]
Myotonic dystrophy type 1	DISJC0OX	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Obesity	DIS47Y1K	Strong	Genetic Variation	[18]
Oral cancer	DISLD42D	Strong	Altered Expression	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Alzheimer disease	DISF8S70	moderate	Genetic Variation	[20]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[21]
Lung cancer	DISCM4YA	moderate	Altered Expression	[22]
Neurofibromatosis type 1	DIS53JH9	moderate	Biomarker	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[24]
Melanoma	DIS1RRCY	Limited	Biomarker	[24]
Myotonic dystrophy	DISNBEMX	Limited	Biomarker	[25]
Myotonic dystrophy type 2	DIS5ZWF1	Limited	Altered Expression	[26]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[27]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CUGBP Elav-like family member 1 (CELF1).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CUGBP Elav-like family member 1 (CELF1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[34]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[35]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CUGBP Elav-like family member 1 (CELF1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of CUGBP Elav-like family member 1 (CELF1).	[38]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of CUGBP Elav-like family member 1 (CELF1).	[39]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[40]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of CUGBP Elav-like family member 1 (CELF1).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CUGBP Elav-like family member 1 (CELF1).	[42]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of CUGBP Elav-like family member 1 (CELF1).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of CUGBP Elav-like family member 1 (CELF1).	[43]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of CUGBP Elav-like family member 1 (CELF1).	[41]

References

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• [2] Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia.Genomics. 2001 Jun 15;74(3):396-401. doi: 10.1006/geno.2001.6558.
• [3] Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1.Oncogene. 2016 Apr 21;35(16):2087-97. doi: 10.1038/onc.2015.271. Epub 2015 Aug 3.
• [4] RNA Binding Protein CUGBP1 Inhibits Liver Cancer in a Phosphorylation-Dependent Manner.Mol Cell Biol. 2017 Jul 28;37(16):e00128-17. doi: 10.1128/MCB.00128-17. Print 2017 Aug 15.
• [5] Gene Expression Analyses during Spontaneous Reversal of Cardiomyopathy in Mice with Repressed Nuclear CUG-BP, Elav-Like Family (CELF) Activity in Heart Muscle.PLoS One. 2015 Apr 20;10(4):e0124462. doi: 10.1371/journal.pone.0124462. eCollection 2015.
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• [7] Lentivirus-mediated knockdown of CUGBP1 suppresses gastric cancer cell proliferation in vitro.Appl Biochem Biotechnol. 2014 Jul;173(6):1529-36. doi: 10.1007/s12010-014-0937-8. Epub 2014 May 13.
• [8] CELF1 is Up-Regulated in Glioma and Promotes Glioma Cell Proliferation by Suppression of CDKN1B.Int J Biol Sci. 2015 Sep 22;11(11):1314-24. doi: 10.7150/ijbs.11344. eCollection 2015.
• [9] Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.PLoS One. 2013 May 7;8(5):e62674. doi: 10.1371/journal.pone.0062674. Print 2013.
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• [15] Smaug/SAMD4A restores translational activity of CUGBP1 and suppresses CUG-induced myopathy.PLoS Genet. 2013 Apr;9(4):e1003445. doi: 10.1371/journal.pgen.1003445. Epub 2013 Apr 18.
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• [17] Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2.BMC Cancer. 2016 Aug 2;16:583. doi: 10.1186/s12885-016-2569-6.
• [18] Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity.Am J Med Genet B Neuropsychiatr Genet. 2014 Jun;165B(4):283-93. doi: 10.1002/ajmg.b.32234. Epub 2014 May 1.
• [19] RNA-binding protein CELF1 promotes tumor growth and alters gene expression in oral squamous cell carcinoma.Oncotarget. 2015 Dec 22;6(41):43620-34. doi: 10.18632/oncotarget.6204.
• [20] The relationship between four GWAS-identified loci in Alzheimer's disease and the risk of Parkinson's disease, amyotrophic lateral sclerosis, and multiple system atrophy.Neurosci Lett. 2018 Nov 1;686:205-210. doi: 10.1016/j.neulet.2018.08.024. Epub 2018 Aug 22.
• [21] Inhibition of CUG-binding protein 1 and activation of caspases are critically involved in piperazine derivative BK10007S induced apoptosis in hepatocellular carcinoma cells.PLoS One. 2017 Oct 16;12(10):e0186490. doi: 10.1371/journal.pone.0186490. eCollection 2017.
• [22] CUGBP1 promotes cell proliferation and suppresses apoptosis via down-regulating C/EBP in human non-small cell lung cancers.Med Oncol. 2015 Mar;32(3):82. doi: 10.1007/s12032-015-0544-8. Epub 2015 Feb 21.
• [23] Alternative splicing of the neurofibromatosis type 1 pre-mRNA is regulated by the muscleblind-like proteins and the CUG-BP and ELAV-like factors.BMC Mol Biol. 2012 Dec 10;13:35. doi: 10.1186/1471-2199-13-35.
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• [25] Mir-206 partially rescues myogenesis deficiency by inhibiting CUGBP1 accumulation in the cell models of myotonic dystrophy.Neurol Res. 2019 Jan;41(1):9-18. doi: 10.1080/01616412.2018.1493963. Epub 2018 Oct 3.
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• [33] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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