Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKES4YR)

• DOT Name: Cytoplasmic polyadenylation element-binding protein 2 (CPEB2)
• Synonyms: CPE-BP2; CPE-binding protein 2; hCPEB-2
• Gene Name: CPEB2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colorectal carcinoma
  Neoplasm
  Triple negative breast cancer
  Nasopharyngeal carcinoma
• UniProt ID: CPEB2_HUMAN
• Pfam ID: PF16366 ; PF16367
• Sequence:
  MPPPSPDSENGFYPGLPSSMNPAFFPSFSPVSPHGCTGLSVPTSGGGGGGFGGPFSATAV
  PPPPPPAMNIPQQQPPPPAAPQQPQSRRSPVSPQLQQQHQAAAAAFLQQRNSYNHHQPLL
  KQSPWSNHQSSGWGTGSMSWGAMHGRDHRRTGNMGIPGTMNQISPLKKPFSGNVIAPPKF
  TRSTPSLTPKSWIEDNVFRTDNNSNTLLPLQVRSSLQLPAWGSDSLQDSWCTAAGTSRID
  QDRSRMYDSLNMHSLENSLIDIMRAEHDPLKGRLSYPHPGTDNLLMLNGRSSLFPIDDGL
  LDDGHSDQVGVLNSPTCYSAHQNGERIERFSRKVFVGGLPPDIDEDEITASFRRFGPLVV
  DWPHKAESKSYFPPKGYAFLLFQEESSVQALIDACIEEDGKLYLCVSSPTIKDKPVQIRP
  WNLSDSDFVMDGSQPLDPRKTIFVGGVPRPLRAVELAMIMDRLYGGVCYAGIDTDPELKY
  PKGAGRVAFSNQQSYIAAISARFVQLQHGDIDKRVEVKPYVLDDQMCDECQGARCGGKFA
  PFFCANVTCLQYYCEFCWANIHSRAGREFHKPLVKEGADRPRQIHFRWN
• Function: May play a role in translational regulation of stored mRNAs in transcriptionally inactive haploid spermatids. Binds to poly(U) RNA oligomers. Required for cell cycle progression, specifically for the transition from metaphase to anaphase.
• KEGG Pathway:
  Oocyte meiosis (hsa04114)
  Progesterone-mediated oocyte maturation (hsa04914)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[5]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[25]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the methylation of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[16]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[19]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[21]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cytoplasmic polyadenylation element-binding protein 2 (CPEB2).	[27]

References

• [1] Splice variants of cytosolic polyadenylation element-binding protein 2 (CPEB2) differentially regulate pathways linked to cancer metastasis.J Biol Chem. 2017 Oct 27;292(43):17909-17918. doi: 10.1074/jbc.M117.810127. Epub 2017 Sep 13.
• [2] Tumor suppressor role of cytoplasmic polyadenylation element binding protein 2 (CPEB2) in human mammary epithelial cells.BMC Cancer. 2019 Jun 11;19(1):561. doi: 10.1186/s12885-019-5771-5.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer.Oncotarget. 2017 Apr 18;8(16):26858-26870. doi: 10.18632/oncotarget.15844.
• [5] Serine/Arginine-Rich Splicing Factor 3 Modulates the Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2.Mol Cancer Res. 2019 Sep;17(9):1920-1930. doi: 10.1158/1541-7786.MCR-18-1291. Epub 2019 May 28.
• [6] LncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis.Cell Cycle. 2017 Apr 18;16(8):795-801. doi: 10.1080/15384101.2017.1301334. Epub 2017 Mar 30.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Estrogen-responsive genes newly found to be modified by TCDD exposure in human cell lines and mouse systems. Mol Cell Endocrinol. 2007 Jun 30;272(1-2):38-49.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [15] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [19] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [20] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [24] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [25] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [26] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [28] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.