Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUJQ3VL)

• DOT Name: Cbp/p300-interacting transactivator 1 (CITED1)
• Synonyms: Melanocyte-specific protein 1
• Gene Name: CITED1
• Related Disease:
  Advanced cancer
  Adenoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Childhood kidney Wilms tumor
  Colorectal carcinoma
  Hypopigmentation of the skin
  Immunodeficiency
  Neoplasm
  Renal dysplasia
  Thyroid gland papillary carcinoma
  Trophoblastic neoplasm
  Wilms tumor
  Fetal growth restriction
  Melanocytic nevus
  Melanoma
  Microphthalmia
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: CITE1_HUMAN
• Pfam ID: PF04487
• Sequence:
  MPTTSRPALDVKGGTSPAKEDANQEMSSVAYSNLAVKDRKAVAILHYPGVASNGTKASGA
  PTSSSGSPIGSPTTTPPTKPPSFNLHPAPHLLASMHLQKLNSQYQGMAAATPGQPGEAGP
  LQNWDFGAQAGGAESLSPSAGAQSPAIIDSDPVDEEVLMSLVVELGLDRANELPELWLGQ
  NEFDFTADFPSSC
• Function: Transcriptional coactivator of the p300/CBP-mediated transcription complex. Enhances SMAD-mediated transcription by strengthening the functional link between the DNA-binding SMAD transcription factors and the p300/CBP transcription coactivator complex. Stimulates estrogen-dependent transactivation activity mediated by estrogen receptors signaling; stabilizes the interaction of estrogen receptor ESR1 and histone acetyltransferase EP300. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Induces transcription from estrogen-responsive promoters and protection against cell death. Potentiates EGR2-mediated transcriptional activation activity from the ERBB2 promoter. Acts as an inhibitor of osteoblastic mineralization through a cAMP-dependent parathyroid hormone receptor signaling. May play a role in pigmentation of melanocytes. Associates with chromatin to the estrogen-responsive TGF-alpha promoter region in a estrogen-dependent manner.
• Tissue Specificity: Expressed only in melanocytes and testis.
• Reactome Pathway:
  Estrogen-dependent gene expression (R-HSA-9018519)
  Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Childhood kidney Wilms tumor	DIS0NMK3	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Hypopigmentation of the skin	DIS39YKC	Strong	Genetic Variation	[6]
Immunodeficiency	DIS093I0	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Renal dysplasia	DIS3DFGD	Strong	Genetic Variation	[8]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[7]
Trophoblastic neoplasm	DISY8WKT	Strong	Altered Expression	[9]
Wilms tumor	DISB6T16	Strong	Biomarker	[4]
Fetal growth restriction	DIS5WEJ5	moderate	Biomarker	[10]
Melanocytic nevus	DISYS32D	Limited	Biomarker	[11]
Melanoma	DIS1RRCY	Limited	Biomarker	[12]
Microphthalmia	DISGEBES	Limited	Altered Expression	[13]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[14]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[14]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[14]

13 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 Cbp/p300-interacting transactivator 1 (CITED1).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[21]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[22]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[23]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Cbp/p300-interacting transactivator 1 (CITED1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[26]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Cbp/p300-interacting transactivator 1 (CITED1).	[27]

References

• [1] CITED1 promotes proliferation of papillary thyroid cancer cells via the regulation of p21 and p27.Cell Biosci. 2018 Nov 6;8:57. doi: 10.1186/s13578-018-0256-9. eCollection 2018.
• [2] Cited1 deficiency suppresses intestinal tumorigenesis.PLoS Genet. 2013;9(8):e1003638. doi: 10.1371/journal.pgen.1003638. Epub 2013 Aug 1.
• [3] ERalpha-CITED1 co-regulated genes expressed during pubertal mammary gland development: implications for breast cancer prognosis.Oncogene. 2007 Sep 27;26(44):6406-19. doi: 10.1038/sj.onc.1210468. Epub 2007 May 7.
• [4] CITED1 confers stemness to Wilms tumor and enhances tumorigenic responses when enriched in the nucleus.Oncotarget. 2014 Jan 30;5(2):386-402. doi: 10.18632/oncotarget.1566.
• [5] Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression.J Surg Res. 2013 Nov;185(1):136-42. doi: 10.1016/j.jss.2013.05.041. Epub 2013 Jun 2.
• [6] msg1, a novel melanocyte-specific gene, encodes a nuclear protein and is associated with pigmentation.Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12298-303. doi: 10.1073/pnas.93.22.12298.
• [7] CITED1 contributes to the progression of papillary thyroid carcinoma via the Wnt/-catenin signaling pathway.Onco Targets Ther. 2019 Aug 21;12:6769-6777. doi: 10.2147/OTT.S215025. eCollection 2019.
• [8] Placental insufficiency associated with loss of Cited1 causes renal medullary dysplasia.J Am Soc Nephrol. 2009 Apr;20(4):777-86. doi: 10.1681/ASN.2008050547. Epub 2009 Mar 18.
• [9] Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling.Cell Death Dis. 2018 Sep 11;9(9):924. doi: 10.1038/s41419-018-0991-1.
• [10] Organ-specific defects in insulin-like growth factor and insulin receptor signaling in late gestational asymmetric intrauterine growth restriction in Cited1 mutant mice.Endocrinology. 2011 Jun;152(6):2503-16. doi: 10.1210/en.2010-1385. Epub 2011 Apr 12.
• [11] Regulation of expression of MSG1 melanocyte-specific nuclear protein in human melanocytes and melanoma cells.Exp Cell Res. 1998 Aug 1;242(2):478-86. doi: 10.1006/excr.1998.4123.
• [12] Melanocyte-specific gene 1 promotes melanoma progression by enhancing the expression of Bcl-2.Oncol Lett. 2018 Feb;15(2):2413-2418. doi: 10.3892/ol.2017.7592. Epub 2017 Dec 12.
• [13] Expression of genes for microphthalmia isoforms, Pax3 and MSG1, in human melanomas.Cell Mol Biol (Noisy-le-grand). 1999 Nov;45(7):1075-82.
• [14] CITED1 gene promotes proliferation, migration and invasion in papillary thyroid cancer.Oncol Lett. 2018 Jul;16(1):105-112. doi: 10.3892/ol.2018.8653. Epub 2018 May 7.
• [15] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [16] 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.
• [17] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [18] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [21] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [22] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [23] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [24] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [25] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [26] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [27] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.