Details of Drug Off-Target (DOT)

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

• DOT Name: Immediate early response gene 5 protein (IER5)
• Gene Name: IER5
• Related Disease:
  Acute myelogenous leukaemia
  Cervical cancer
  Cervical carcinoma
  Neoplasm
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: IER5_HUMAN
• Pfam ID: PF05760
• Sequence:
  MEFKLEAHRIVSISLGKIYNSRVQRGGIKLHKNLLVSLVLRSARQVYLSDPCPGLYLAGP
  AGTPAPPPQQQPGEPAAGPPAGWGEPPPPAARASWPETEPQPERSSVSDAPRVGDEVPVA
  TVTGVGDVFQGGEADATEAAWSRVEGPRQAAAREAEGTAGGWGVFPEVSRAARRPCGCPL
  GGEDPPGTPAATPRAACCCAPQPAEDEPPAPPAVCPRKRCAAGVGGGPAGCPAPGSTPLK
  KPRRNLEQPPSGGEDDDAEEMETGNVANLISIFGSSFSGLLRKSPGGGREEEEGEESGPE
  AAEPGQICCDKPVLRDMNPWSTAIVAF
• Function: Plays a role as a transcription factor. Mediates positive transcriptional regulation of several chaperone genes during the heat shock response in a HSF1-dependent manner. Mediates negative transcriptional regulation of CDC25B expression. Plays a role in the dephosphorylation of the heat shock factor HSF1 and ribosomal protein S6 kinase (S6K) by the protein phosphatase PP2A. Involved in the regulation of cell proliferation and resistance to thermal stress. Involved in the cell cycle checkpoint and survival in response to ionizing radiation. Associates with chromatin to the CDC25B promoter.
• Tissue Specificity: Expressed in acute myeloid leukemia (AML) cells.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Posttranslational Modification	[4]
Liver cancer	DISDE4BI	Limited	Posttranslational Modification	[4]

23 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 Immediate early response gene 5 protein (IER5).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Immediate early response gene 5 protein (IER5).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Immediate early response gene 5 protein (IER5).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Immediate early response gene 5 protein (IER5).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Immediate early response gene 5 protein (IER5).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Immediate early response gene 5 protein (IER5).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Immediate early response gene 5 protein (IER5).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Immediate early response gene 5 protein (IER5).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Immediate early response gene 5 protein (IER5).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Immediate early response gene 5 protein (IER5).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Immediate early response gene 5 protein (IER5).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Immediate early response gene 5 protein (IER5).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Immediate early response gene 5 protein (IER5).	[16]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Immediate early response gene 5 protein (IER5).	[17]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Immediate early response gene 5 protein (IER5).	[17]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Immediate early response gene 5 protein (IER5).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Immediate early response gene 5 protein (IER5).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Immediate early response gene 5 protein (IER5).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Immediate early response gene 5 protein (IER5).	[20]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide affects the expression of Immediate early response gene 5 protein (IER5).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Immediate early response gene 5 protein (IER5).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Immediate early response gene 5 protein (IER5).	[23]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Immediate early response gene 5 protein (IER5).	[24]

References

• [1] Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of leukemic progenitor cells through NF-YB and p300 in acute myeloid leukemia.PLoS One. 2011;6(11):e28011. doi: 10.1371/journal.pone.0028011. Epub 2011 Nov 23.
• [2] IER5 as a promising predictive marker promotes irradiation-induced apoptosis in cervical cancer tissues from patients undergoing chemoradiotherapy.Oncotarget. 2017 May 30;8(22):36438-36448. doi: 10.18632/oncotarget.16857.
• [3] IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis.Sci Rep. 2016 Jan 12;6:19174. doi: 10.1038/srep19174.
• [4] Transcriptional regulation of IER5 in response to radiation in HepG2.Cancer Gene Ther. 2016 Feb-Mar;23(2-3):61-5. doi: 10.1038/cgt.2016.1. Epub 2016 Feb 26.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] 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.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] p53 hypersensitivity is the predominant mechanism of the unique responsiveness of testicular germ cell tumor (TGCT) cells to cisplatin. PLoS One. 2011 Apr 21;6(4):e19198. doi: 10.1371/journal.pone.0019198.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] 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.
• [13] 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.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [17] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [20] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [21] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [22] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [23] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [24] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.