Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUKXP1E)

• DOT Name: Periodic tryptophan protein 1 homolog (PWP1)
• Synonyms: Keratinocyte protein IEF SSP 9502
• Gene Name: PWP1
• Related Disease:
  Psoriasis
  Head-neck squamous cell carcinoma
  Neoplasm
• UniProt ID: PWP1_HUMAN
• Pfam ID: PF00400
• Sequence:
  MNRSRQVTCVAWVRCGVAKETPDKVELSKEEVKRLIAEAKEKLQEEGGGSDEEETGSPSE
  DGMQSARTQARPREPLEDGDPEDDRTLDDDELAEYDLDKYDEEGDPDAETLGESLLGLTV
  YGSNDQDPYVTLKDTEQYEREDFLIKPSDNLIVCGRAEQDQCNLEVHVYNQEEDSFYVHH
  DILLSAYPLSVEWLNFDPSPDDSTGNYIAVGNMTPVIEVWDLDIVDSLEPVFTLGSKLSK
  KKKKKGKKSSSAEGHTDAVLDLSWNKLIRNVLASASADNTVILWDMSLGKPAASLAVHTD
  KVQTLQFHPFEAQTLISGSYDKSVALYDCRSPDESHRMWRFSGQIERVTWNHFSPCHFLA
  STDDGFVYNLDARSDKPIFTLNAHNDEISGLDLSSQIKGCLVTASADKYVKIWDILGDRP
  SLVHSRDMKMGVLFCSSCCPDLPFIYAFGGQKEGLRVWDISTVSSVNEAFGRRERLVLGS
  ARNSSISGPFGSRSSDTPMES
• Function: Chromatin-associated factor that regulates transcription. Regulates Pol I-mediated rRNA biogenesis and, probably, Pol III-mediated transcription. Regulates the epigenetic status of rDNA.
• Tissue Specificity: High levels seen in the placenta, skeletal muscle, kidney and pancreas while lower levels were seen in the heart, brain and lung.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriasis	DIS59VMN	Strong	Biomarker	[1]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[2]
Neoplasm	DISZKGEW	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Periodic tryptophan protein 1 homolog (PWP1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Periodic tryptophan protein 1 homolog (PWP1).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[11]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[14]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[15]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Periodic tryptophan protein 1 homolog (PWP1).	[16]

1 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 decreases the methylation of Periodic tryptophan protein 1 homolog (PWP1).	[13]

References

• [1] Evidence on the direct correlation between miR-31 and IL-22 axis in IMQ-induced psoriasis.Exp Dermatol. 2019 Nov;28(11):1336-1340. doi: 10.1111/exd.14001. Epub 2019 Oct 22.
• [2] PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of Ribosomal Gene Expression.Dev Cell. 2017 Oct 23;43(2):240-252.e5. doi: 10.1016/j.devcel.2017.09.022.
• [3] 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.
• [4] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [5] 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.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [11] 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.
• [12] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [13] 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.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [15] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [16] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.