Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOXUDV1)

• DOT Name: TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D)
• Synonyms: RNA polymerase I-specific TBP-associated factor 41 kDa; TAFI41; TATA box-binding protein-associated factor 1D; TBP-associated factor 1D; Transcription initiation factor SL1/TIF-IB subunit D
• Gene Name: TAF1D
• Related Disease: Skin disease
• UniProt ID: TAF1D_HUMAN
• Pfam ID: PF15333
• Sequence:
  MDKSGIDSLDHVTSDAVELANRSDNSSDSSLFKTQCIPYSPKGEKRNPIRKFVRTPESVH
  ASDSSSDSSFEPIPLTIKAIFERFKNRKKRYKKKKKRRYQPTGRPRGRPEGRRNPIYSLI
  DKKKQFRSRGSGFPFLESENEKNAPWRKILTFEQAVARGFFNYIEKLKYEHHLKESLKQM
  NVGEDLENEDFDSRRYKFLDDDGSISPIEESTAEDEDATHLEDNECDIKLAGDSFIVSSE
  FPVRLSVYLEEEDITEEAALSKKRATKAKNTGQRGLKM
• Function: Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  B-WICH complex positively regulates rRNA expression (R-HSA-5250924)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  RNA Polymerase I Promoter Escape (R-HSA-73772)
  RNA Polymerase I Transcription Termination (R-HSA-73863)
  SIRT1 negatively regulates rRNA expression (R-HSA-427359)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Skin disease	DISDW8R6	Strong	Biomarker	[1]

15 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 TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[1]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[16]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of TATA box-binding protein-associated factor RNA polymerase I subunit D (TAF1D).	[13]

References

• [1] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [6] 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.
• [7] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [8] 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.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] 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.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.