Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1XVNDP)

• DOT Name: p53-regulated apoptosis-inducing protein 1 (TP53AIP1)
• Synonyms: p53AIP1
• Gene Name: TP53AIP1
• Related Disease:
  Cutaneous melanoma
  Melanoma
  Prostate cancer
  Prostate carcinoma
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Gastric cancer
  Stomach cancer
  Advanced cancer
  Neoplasm
• UniProt ID: TPIP1_HUMAN
• Pfam ID: PF15338
• Sequence:
  MGSSSEASFRSAQASCSGARRQGLGRGDQNLSVMPPNGRAQTHTPGWVSDPLVLGAQVHG
  GCRGIEALSVSSGSWSSATVWILTGLGLGLSRPFLPGATVLRDRPLGSAFELSYDQKKAP
  LRLQ
• Function: May play an important role in mediating p53/TP53-dependent apoptosis.
• Tissue Specificity: Only found to be expressed in thymus.
• KEGG Pathway:
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutaneous melanoma	DIS3MMH9	Definitive	Genetic Variation	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Prostate cancer	DISF190Y	Definitive	Genetic Variation	[1]
Prostate carcinoma	DISMJPLE	Definitive	Genetic Variation	[1]
B-cell neoplasm	DISVY326	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[4]
Lung neoplasm	DISVARNB	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[6]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of p53-regulated apoptosis-inducing protein 1 (TP53AIP1).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of p53-regulated apoptosis-inducing protein 1 (TP53AIP1).	[9]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of p53-regulated apoptosis-inducing protein 1 (TP53AIP1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of p53-regulated apoptosis-inducing protein 1 (TP53AIP1).	[12]

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 increases the methylation of p53-regulated apoptosis-inducing protein 1 (TP53AIP1).	[11]

References

• [1] Truncating mutations of TP53AIP1 gene predispose to cutaneous melanoma.Genes Chromosomes Cancer. 2018 Jun;57(6):294-303. doi: 10.1002/gcc.22528. Epub 2018 Feb 21.
• [2] Overexpression of Tumor Protein p53-regulated Apoptosis-inducing Protein 1 Regulates Proliferation and Apoptosis of Breast Cancer Cells through the PI3K/Akt Pathway.J Breast Cancer. 2019 Jun;22(2):172-184. doi: 10.4048/jbc.2019.22.e21.
• [3] Altered binding site selection of p53 transcription cassettes by hepatitis B virus X protein.Mol Cell Biol. 2013 Feb;33(3):485-97. doi: 10.1128/MCB.01189-12. Epub 2012 Nov 12.
• [4] Combination of p53AIP1 and survivin expression is a powerful prognostic marker in non-small cell lung cancer.J Exp Clin Cancer Res. 2009 Feb 19;28(1):22. doi: 10.1186/1756-9966-28-22.
• [5] p53AIP1 expression can be a prognostic marker in non-small cell lung cancer.Clin Oncol (R Coll Radiol). 2008 Mar;20(2):148-51. doi: 10.1016/j.clon.2007.08.006. Epub 2007 Sep 12.
• [6] Difference of p53AIP1 mRNA expression in gastric mucosa between patients with gastric cancer and chronic gastritis infected with Helicobacter pylori.J Clin Gastroenterol. 2008 Apr;42(4):351-5. doi: 10.1097/MCG.0b013e318054493e.
• [7] Extracellular vesicledelivered miR?05?p, as a diagnostic biomarker of early lung adenocarcinoma, inhibits cell apoptosis by targeting TP53AIP1.Int J Oncol. 2019 May;54(5):1821-1832. doi: 10.3892/ijo.2019.4738. Epub 2019 Mar 1.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.