Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW35WKX)

• DOT Name: Jun dimerization protein 2 (JDP2)
• Gene Name: JDP2
• Related Disease:
  Neoplasm
  Nervous system disease
  Adrenocortical carcinoma
  Advanced cancer
  Cardiac failure
  Congestive heart failure
  Glioma
  Hepatocellular carcinoma
  Malignant tumor of adrenal cortex
  Metastatic malignant neoplasm
  Myocardial infarction
  T-cell acute lymphoblastic leukaemia
  Acute myelogenous leukaemia
  Amyotrophic lateral sclerosis
  Basal cell carcinoma
  Basal cell neoplasm
  Pancreatic cancer
• UniProt ID: JDP2_HUMAN
• Pfam ID: PF00170
• Sequence:
  MMPGQIPDPSVTTGSLPGLGPLTGLPSSALTVEELKYADIRNLGAMIAPLHFLEVKLGKR
  PQPVKSELDEEEERRKRRREKNKVAAARCRNKKKERTEFLQRESERLELMNAELKTQIEE
  LKQERQQLILMLNRHRPTCIVRTDSVKTPESEGNPLLEQLEKK
• Function: Component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Involved in a variety of transcriptional responses associated with AP-1 such as UV-induced apoptosis, cell differentiation, tumorigenesis and antitumogeneris. Can also function as a repressor by recruiting histone deacetylase 3/HDAC3 to the promoter region of JUN. May control transcription via direct regulation of the modification of histones and the assembly of chromatin.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[2]
Adrenocortical carcinoma	DISZF4HX	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Malignant tumor of adrenal cortex	DIS7E0I8	Strong	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[7]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[8]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[9]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[10]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[11]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[11]
Pancreatic cancer	DISJC981	Limited	Biomarker	[12]

20 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 Jun dimerization protein 2 (JDP2).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Jun dimerization protein 2 (JDP2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Jun dimerization protein 2 (JDP2).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Jun dimerization protein 2 (JDP2).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Jun dimerization protein 2 (JDP2).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Jun dimerization protein 2 (JDP2).	[18]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Jun dimerization protein 2 (JDP2).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Jun dimerization protein 2 (JDP2).	[20]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Jun dimerization protein 2 (JDP2).	[21]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Jun dimerization protein 2 (JDP2).	[22]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Jun dimerization protein 2 (JDP2).	[23]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Jun dimerization protein 2 (JDP2).	[24]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Jun dimerization protein 2 (JDP2).	[25]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Jun dimerization protein 2 (JDP2).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Jun dimerization protein 2 (JDP2).	[26]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Jun dimerization protein 2 (JDP2).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Jun dimerization protein 2 (JDP2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Jun dimerization protein 2 (JDP2).	[27]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Jun dimerization protein 2 (JDP2).	[29]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Jun dimerization protein 2 (JDP2).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Jun dimerization protein 2 (JDP2).	[28]

References

• [1] COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status.BMC Cancer. 2011 Jun 13;11:238. doi: 10.1186/1471-2407-11-238.
• [2] Deletion of JDP2 improves neurological outcomes of traumatic brain injury (TBI) in mice: Inactivation of Caspase-3.Biochem Biophys Res Commun. 2018 Oct 12;504(4):805-811. doi: 10.1016/j.bbrc.2018.08.055. Epub 2018 Sep 11.
• [3] Jun Dimerization Protein 2 Activates Mc2r Transcriptional Activity: Role of Phosphorylation and SUMOylation.Int J Mol Sci. 2017 Jan 31;18(2):304. doi: 10.3390/ijms18020304.
• [4] JDP2 overexpression provokes cardiac dysfunction in mice.Sci Rep. 2018 May 16;8(1):7647. doi: 10.1038/s41598-018-26052-w.
• [5] The -catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.Oncotarget. 2017 Apr 18;8(16):27300-27313. doi: 10.18632/oncotarget.15934.
• [6] miR-501 acts as an independent prognostic factor that promotes the epithelial-mesenchymal transition through targeting JDP2 in hepatocellular carcinoma.Hum Cell. 2019 Jul;32(3):343-351. doi: 10.1007/s13577-019-00243-7. Epub 2019 Mar 15.
• [7] Downregulation of AP-1 repressor JDP2 is associated with tumor metastasis and poor prognosis in patients with pancreatic carcinoma.Int J Biol Markers. 2010 Jul-Sep;25(3):136-40. doi: 10.1177/172460081002500303.
• [8] JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia.J Exp Med. 2018 Jul 2;215(7):1929-1945. doi: 10.1084/jem.20170484. Epub 2018 Jun 25.
• [9] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [10] Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK and JDP2 in NSC-34 cells.Genet Mol Res. 2017 May 10;16(2). doi: 10.4238/gmr16029638.
• [11] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [12] The effect of JDP2 and ATF2 on the epithelial-mesenchymal transition of human pancreatic cancer cell lines.Pathol Oncol Res. 2012 Jul;18(3):571-7. doi: 10.1007/s12253-011-9476-6. Epub 2011 Nov 23.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] 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.
• [15] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [18] Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology. 2008 Oct;149(10):4809-20. doi: 10.1210/en.2008-0035. Epub 2008 Jun 12.
• [19] 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.
• [20] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [23] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [24] 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.
• [25] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [26] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [27] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [28] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [29] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [30] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.