Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW1SCZW)

• DOT Name: Cytoplasmic polyadenylation element-binding protein 4 (CPEB4)
• Synonyms: CPE-BP4; CPE-binding protein 4; hCPEB-4
• Gene Name: CPEB4
• Related Disease:
  Liver cirrhosis
  Adult glioblastoma
  Advanced cancer
  Autism spectrum disorder
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Malignant glioma
  Metastatic malignant neoplasm
  Non-alcoholic fatty liver disease
  Pancreatic ductal carcinoma
  Patent ductus arteriosus
  Seasonal allergic rhinitis
  Carcinoma of liver and intrahepatic biliary tract
  Head-neck squamous cell carcinoma
  Inflammatory bowel disease
  Liver cancer
  Adenocarcinoma
  Ankylosing spondylitis
  Crohn disease
  Gallbladder cancer
  Gallbladder carcinoma
  Gastric cancer
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Psoriasis
  Sclerosing cholangitis
  Stomach cancer
  Ulcerative colitis
• UniProt ID: CPEB4_HUMAN
• PDB ID: 2MKI; 2MKJ; 5DIF
• Pfam ID: PF16366 ; PF16367
• Sequence:
  MGDYGFGVLVQSNTGNKSAFPVRFHPHLQPPHHHQNATPSPAAFINNNTAANGSSAGSAW
  LFPAPATHNIQDEILGSEKAKSQQQEQQDPLEKQQLSPSPGQEAGILPETEKAKSEENQG
  DNSSENGNGKEKIRIESPVLTGFDYQEATGLGTSTQPLTSSASSLTGFSNWSAAIAPSSS
  TIINEDASFFHQGGVPAASANNGALLFQNFPHHVSPGFGGSFSPQIGPLSQHHPHHPHFQ
  HHHSQHQQQRRSPASPHPPPFTHRNAAFNQLPHLANNLNKPPSPWSSYQSPSPTPSSSWS
  PGGGGYGGWGGSQGRDHRRGLNGGITPLNSISPLKKNFASNHIQLQKYARPSSAFAPKSW
  MEDSLNRADNIFPFPDRPRTFDMHSLESSLIDIMRAENDTIKGRLNYSYPGSDSSLLINA
  RTYGRRRGQSSLFPMEDGFLDDGRGDQPLHSGLGSPHCFSHQNGERVERYSRKVFVGGLP
  PDIDEDEITASFRRFGPLIVDWPHKAESKSYFPPKGYAFLLFQDESSVQALIDACIEEDG
  KLYLCVSSPTIKDKPVQIRPWNLSDSDFVMDGSQPLDPRKTIFVGGVPRPLRAVELAMIM
  DRLYGGVCYAGIDTDPELKYPKGAGRVAFSNQQSYIAAISARFVQLQHGEIDKRVEVKPY
  VLDDQLCDECQGARCGGKFAPFFCANVTCLQYYCEYCWAAIHSRAGREFHKPLVKEGGDR
  PRHISFRWN
• Function: Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism. Regulates activation of unfolded protein response (UPR) in the process of adaptation to ER stress in liver, by maintaining translation of CPE-regulated mRNAs in conditions in which global protein synthesis is inhibited. Required for cell cycle progression, specifically for cytokinesis and chromosomal segregation. Plays a role as an oncogene promoting tumor growth and progression by positively regulating translation of t-plasminogen activator/PLAT. Stimulates proliferation of melanocytes. In contrast to CPEB1 and CPEB3, does not play role in synaptic plasticity, learning and memory.
• Tissue Specificity: Expressed in pancreas in islets and ductal cells (at protein level) . Expressed in melanocytes .
• KEGG Pathway:
  Oocyte meiosis (hsa04114)
  Progesterone-mediated oocyte maturation (hsa04914)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Liver cirrhosis	DIS4G1GX	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Malignant glioma	DISFXKOV	Strong	Genetic Variation	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[5]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[9]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Biomarker	[7]
Patent ductus arteriosus	DIS9P8YS	Strong	Biomarker	[7]
Seasonal allergic rhinitis	DIS58KQX	Strong	Biomarker	[10]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Altered Expression	[11]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[12]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[13]
Liver cancer	DISDE4BI	moderate	Altered Expression	[11]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[14]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[15]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[15]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[16]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[16]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[17]
Melanoma	DIS1RRCY	Limited	Biomarker	[18]
Neoplasm	DISZKGEW	Limited	Altered Expression	[12]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[19]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[15]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[15]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[17]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[24]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[25]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[27]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[28]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[29]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[30]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[33]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[34]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[36]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[39]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[40]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[41]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cytoplasmic polyadenylation element-binding protein 4 (CPEB4).	[35]

References

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• [17] CPEB4 promotes growth and metastasis of gastric cancer cells via ZEB1-mediated epithelial- mesenchymal transition.Onco Targets Ther. 2018 Sep 21;11:6153-6165. doi: 10.2147/OTT.S175428. eCollection 2018.
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• [19] Knockdown of CPEB4 expression suppresses cell migration and invasion via Akt pathway in non-small cell lung cancer.Cell Biol Int. 2018 Nov;42(11):1484-1491. doi: 10.1002/cbin.10930. Epub 2018 Feb 1.
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• [37] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
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