Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUH8IPS)

• DOT Name: RBPJ-interacting and tubulin-associated protein 1 (RITA1)
• Synonyms: RBPJ-interacting and tubulin-associated protein
• Gene Name: RITA1
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Ewing sarcoma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Malignant soft tissue neoplasm
  Matthew-Wood syndrome
  Medulloblastoma
  Neoplasm
  Non-small-cell lung cancer
  Plasma cell myeloma
  Sarcoma
  Thyroid tumor
  Acute myelogenous leukaemia
  Gastrointestinal stromal tumour
  Rhabdomyosarcoma
  Small lymphocytic lymphoma
  Neuroblastoma
• UniProt ID: RITA1_HUMAN
• PDB ID: 5EG6
• Pfam ID: PF17066
• Sequence:
  MKTPVELAVSGMQTLGLQHRCRGGYRVKARTSYVDETLFGSPAGTRPTPPDFDPPWVEKA
  NRTRGVGKEASKALGAKGSCETTPSRGSTPTLTPRKKNKYRPISHTPSYCDESLFGSRSE
  GASFGAPRMAKGDAAKLRALLWTPPPTPRGSHSPRPREAPLRAIHPAGPSKTEPGPAADS
  QKLSMGGLHSSRPLKRGLSHSLTHLNVPSTGHPATSAPHTNGPQDLRPSTSGVTFRSPLV
  TSRARSVSISVPSTPRRGGATQKPKPPWK
• Function: Tubulin-binding protein that acts as a negative regulator of Notch signaling pathway. Shuttles between the cytoplasm and the nucleus and mediates the nuclear export of RBPJ/RBPSUH, thereby preventing the interaction between RBPJ/RBPSUH and NICD product of Notch proteins (Notch intracellular domain), leading to down-regulate Notch-mediated transcription. May play a role in neurogenesis.

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[3]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[4]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[4]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[3]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[7]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[11]
Sarcoma	DISZDG3U	Strong	Biomarker	[3]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[12]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[13]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[14]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[8]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[13]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RBPJ-interacting and tubulin-associated protein 1 (RITA1).	[22]

References

• [1] RITA enhances irradiation-induced apoptosis in p53-defective cervical cancer cells via upregulation of IRE1/XBP1 signaling.Oncol Rep. 2015 Sep;34(3):1279-88. doi: 10.3892/or.2015.4083. Epub 2015 Jun 25.
• [2] Mdm2-P53 Interaction Inhibitor with Cisplatin Enhances Apoptosis in Colon and Prostate Cancer Cells In-Vitro.Asian Pac J Cancer Prev. 2019 Nov 1;20(11):3341-3351. doi: 10.31557/APJCP.2019.20.11.3341.
• [3] IGF-1R/MDM2 relationship confers enhanced sensitivity to RITA in Ewing sarcoma cells.Mol Cancer Ther. 2012 Jun;11(6):1247-56. doi: 10.1158/1535-7163.MCT-11-0913. Epub 2012 Mar 28.
• [4] RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.Redox Biol. 2017 Oct;13:219-227. doi: 10.1016/j.redox.2017.05.025. Epub 2017 Jun 1.
• [5] The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells.PLoS One. 2014 Aug 13;9(8):e104821. doi: 10.1371/journal.pone.0104821. eCollection 2014.
• [6] RBP-J-interacting and tubulin-associated protein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma by activating the p53-Fbxw7 pathway.Biochem Biophys Res Commun. 2014 Nov 7;454(1):71-7. doi: 10.1016/j.bbrc.2014.10.023. Epub 2014 Oct 14.
• [7] Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine.Biochim Biophys Acta. 2015 Jan;1853(1):89-100. doi: 10.1016/j.bbamcr.2014.10.003. Epub 2014 Oct 13.
• [8] RITA downregulates Hedgehog-GLI in medulloblastoma and rhabdomyosarcoma via JNK-dependent but p53-independent mechanism.Cancer Lett. 2019 Feb 1;442:341-350. doi: 10.1016/j.canlet.2018.11.005. Epub 2018 Nov 14.
• [9] Clonal analyses of refractory testicular germ cell tumors.PLoS One. 2019 Mar 14;14(3):e0213815. doi: 10.1371/journal.pone.0213815. eCollection 2019.
• [10] Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells.Cell Physiol Biochem. 2017;42(3):1177-1191. doi: 10.1159/000478873. Epub 2017 Jun 30.
• [11] RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses.Mol Cancer Ther. 2010 Nov;9(11):3041-51. doi: 10.1158/1535-7163.MCT-10-0471. Epub 2010 Nov 9.
• [12] A KRAB zinc finger protein gene is the potential target of 19q13 translocation in benign thyroid tumors.Genes Chromosomes Cancer. 1999 Nov;26(3):229-36.
• [13] Mutated and non-mutated TP53 as targets in the treatment of leukaemia.Br J Haematol. 2008 May;141(4):445-53. doi: 10.1111/j.1365-2141.2008.07046.x. Epub 2008 Mar 12.
• [14] p53 modulation as a therapeutic strategy in gastrointestinal stromal tumors.PLoS One. 2012;7(5):e37776. doi: 10.1371/journal.pone.0037776. Epub 2012 May 25.
• [15] Dual targeting of wild-type and mutant p53 by small molecule RITA results in the inhibition of N-Myc and key survival oncogenes and kills neuroblastoma cells in vivo and in vitro.Clin Cancer Res. 2013 Sep 15;19(18):5092-103. doi: 10.1158/1078-0432.CCR-12-2211. Epub 2013 Jul 17.
• [16] 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.
• [17] 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.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] 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.
• [20] 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.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.