Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3UKHPI)

• DOT Name: Cip1-interacting zinc finger protein (CIZ1)
• Synonyms: CDKN1A-interacting zinc finger protein 1; Nuclear protein NP94; Zinc finger protein 356
• Gene Name: CIZ1
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Hemangioma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Lymphoproliferative syndrome
  Medulloblastoma
  Paroxysmal dystonia
  Prostate cancer
  Prostate neoplasm
  Bladder cancer
  Dystonia 23
  Lung neoplasm
  Neoplasm
  Small-cell lung cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Rheumatoid arthritis
  Carcinoma
  Ewing sarcoma
  Gallbladder cancer
  Gallbladder carcinoma
  Inherited dystonia
  Prostate carcinoma
• UniProt ID: CIZ1_HUMAN
• PDB ID: 7X39
• Pfam ID: PF12171
• Sequence:
  MFSQQQQQQLQQQQQQLQQLQQQQLQQQQLQQQQLLQLQQLLQQSPPQAPLPMAVSRGLP
  PQQPQQPLLNLQGTNSASLLNGSMLQRALLLQQLQGLDQFAMPPATYDTAGLTMPTATLG
  NLRGYGMASPGLAAPSLTPPQLATPNLQQFFPQATRQSLLGPPPVGVPMNPSQFNLSGRN
  PQKQARTSSSTTPNRKDSSSQTMPVEDKSDPPEGSEEAAEPRMDTPEDQDLPPCPEDIAK
  EKRTPAPEPEPCEASELPAKRLRSSEEPTEKEPPGQLQVKAQPQARMTVPKQTQTPDLLP
  EALEAQVLPRFQPRVLQVQAQVQSQTQPRIPSTDTQVQPKLQKQAQTQTSPEHLVLQQKQ
  VQPQLQQEAEPQKQVQPQVQPQAHSQGPRQVQLQQEAEPLKQVQPQVQPQAHSQPPRQVQ
  LQLQKQVQTQTYPQVHTQAQPSVQPQEHPPAQVSVQPPEQTHEQPHTQPQVSLLAPEQTP
  VVVHVCGLEMPPDAVEAGGGMEKTLPEPVGTQVSMEEIQNESACGLDVGECENRAREMPG
  VWGAGGSLKVTILQSSDSRAFSTVPLTPVPRPSDSVSSTPAATSTPSKQALQFFCYICKA
  SCSSQQEFQDHMSEPQHQQRLGEIQHMSQACLLSLLPVPRDVLETEDEEPPPRRWCNTCQ
  LYYMGDLIQHRRTQDHKIAKQSLRPFCTVCNRYFKTPRKFVEHVKSQGHKDKAKELKSLE
  KEIAGQDEDHFITVDAVGCFEGDEEEEEDDEDEEEIEVEEELCKQVRSRDISREEWKGSE
  TYSPNTAYGVDFLVPVMGYICRICHKFYHSNSGAQLSHCKSLGHFENLQKYKAAKNPSPT
  TRPVSRRCAINARNALTALFTSSGRPPSQPNTQDKTPSKVTARPSQPPLPRRSTRLKT
• Function: May regulate the subcellular localization of CIP/WAF1.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Hemangioma	DISDCGAG	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[1]
Lymphoproliferative syndrome	DISMVL8O	Strong	Biomarker	[7]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[8]
Paroxysmal dystonia	DISV0MSQ	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[10]
Bladder cancer	DISUHNM0	moderate	Biomarker	[11]
Dystonia 23	DISY3Q3K	Moderate	Unknown	[12]
Lung neoplasm	DISVARNB	moderate	Biomarker	[13]
Neoplasm	DISZKGEW	moderate	Biomarker	[1]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[13]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[11]
Rheumatoid arthritis	DISTSB4J	Disputed	Altered Expression	[14]
Carcinoma	DISH9F1N	Limited	Altered Expression	[15]
Ewing sarcoma	DISQYLV3	Limited	Biomarker	[16]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[17]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[17]
Inherited dystonia	DISEIJV9	Limited	Autosomal dominant	[18]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[15]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Cip1-interacting zinc finger protein (CIZ1) affects the response to substance of Methotrexate.	[34]

12 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 Cip1-interacting zinc finger protein (CIZ1).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cip1-interacting zinc finger protein (CIZ1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cip1-interacting zinc finger protein (CIZ1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cip1-interacting zinc finger protein (CIZ1).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cip1-interacting zinc finger protein (CIZ1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cip1-interacting zinc finger protein (CIZ1).	[24]
Selenium	DM25CGV	Approved	Selenium increases the expression of Cip1-interacting zinc finger protein (CIZ1).	[25]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Cip1-interacting zinc finger protein (CIZ1).	[26]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Cip1-interacting zinc finger protein (CIZ1).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cip1-interacting zinc finger protein (CIZ1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cip1-interacting zinc finger protein (CIZ1).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cip1-interacting zinc finger protein (CIZ1).	[32]

3 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 affects the methylation of Cip1-interacting zinc finger protein (CIZ1).	[28]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Cip1-interacting zinc finger protein (CIZ1).	[30]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Cip1-interacting zinc finger protein (CIZ1).	[33]

References

• [1] CDKN1A-interacting zinc finger protein 1 is a novel biomarker for lung squamous cell carcinoma.Oncol Lett. 2018 Jan;15(1):183-188. doi: 10.3892/ol.2017.7282. Epub 2017 Oct 26.
• [2] Ciz1, a Novel DNA-binding coactivator of the estrogen receptor alpha, confers hypersensitivity to estrogen action.Cancer Res. 2006 Nov 15;66(22):11021-9. doi: 10.1158/0008-5472.CAN-06-2336.
• [3] CIZ1 regulates the proliferation, cycle distribution and colony formation of RKO human colorectal cancer cells.Mol Med Rep. 2013 Dec;8(6):1630-4. doi: 10.3892/mmr.2013.1716. Epub 2013 Oct 8.
• [4] CIZ1 Expression Is Upregulated in Hemangioma of the Tongue.Pathol Oncol Res. 2019 Oct;25(4):1653-1658. doi: 10.1007/s12253-018-0495-4. Epub 2018 Nov 19.
• [5] CIZ1 interacts with YAP and activates its transcriptional activity in hepatocellular carcinoma cells.Tumour Biol. 2016 Aug;37(8):11073-9. doi: 10.1007/s13277-016-4866-8. Epub 2016 Feb 23.
• [6] Examining transcriptional changes to DNA replication and repair factors over uveal melanoma subtypes.BMC Cancer. 2018 Aug 14;18(1):818. doi: 10.1186/s12885-018-4705-y.
• [7] The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory.Genes Dev. 2017 May 1;31(9):876-888. doi: 10.1101/gad.295907.117. Epub 2017 May 25.
• [8] Ciz1, Cip1 interacting zinc finger protein 1 binds the consensus DNA sequence ARYSR(0-2)YYAC.J Biomed Sci. 2003 Jul-Aug;10(4):406-17. doi: 10.1007/BF02256432.
• [9] Mutations in GNAL cause primary torsion dystonia. Nat Genet. 2013 Jan;45(1):88-92. doi: 10.1038/ng.2496. Epub 2012 Dec 9.
• [10] The bromodomain protein BRD4 regulates the KEAP1/NRF2-dependent oxidative stress response.Cell Death Dis. 2014 Apr 24;5(4):e1195. doi: 10.1038/cddis.2014.157.
• [11] CIZ1 knockdown suppresses the proliferation of bladder cancer cells by inducing apoptosis.Gene. 2019 Nov 30;719:143946. doi: 10.1016/j.gene.2019.143946. Epub 2019 Jun 25.
• [12] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [13] Variant Ciz1 is a circulating biomarker for early-stage lung cancer.Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):E3128-35. doi: 10.1073/pnas.1210107109. Epub 2012 Oct 16.
• [14] The Role of Cdkn1A-Interacting Zinc Finger Protein 1 (CIZ1) in DNA Replication and Pathophysiology.Int J Mol Sci. 2016 Feb 5;17(2):212. doi: 10.3390/ijms17020212.
• [15] Ciz1 promotes tumorigenicity of prostate carcinoma cells.Front Biosci (Landmark Ed). 2015 Jan 1;20(4):705-15. doi: 10.2741/4331.
• [16] Cancer-associated missplicing of exon 4 influences the subnuclear distribution of the DNA replication factor CIZ1.Hum Mutat. 2007 Oct;28(10):993-1004. doi: 10.1002/humu.20550.
• [17] CIZ1 promoted the growth and migration of gallbladder cancer cells.Tumour Biol. 2015 Apr;36(4):2583-91. doi: 10.1007/s13277-014-2876-y. Epub 2014 Nov 28.
• [18] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [19] 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.
• [20] 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.
• [21] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [22] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [23] 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.
• [24] 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.
• [25] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [26] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [27] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [28] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [29] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [30] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [31] 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.
• [32] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [33] 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.
• [34] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.