Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7B0SIB)

• DOT Name: Large ribosomal subunit protein P1 (RPLP1)
• Synonyms: 60S acidic ribosomal protein P1
• Gene Name: RPLP1
• Related Disease:
  Cholangiocarcinoma
  Colon cancer
  Colon carcinoma
  Advanced cancer
  Metastatic malignant neoplasm
  Triple negative breast cancer
• UniProt ID: RLA1_HUMAN
• PDB ID: 2LBF; 4BEH; 4V6X
• Pfam ID: PF00428
• Sequence:
  MASVSELACIYSALILHDDEVTVTEDKINALIKAAGVNVEPFWPGLFAKALANVNIGSLI
  CNVGAGGPAPAAGAAPAGGPAPSTAAAPAEEKKVEAKKEESEESDDDMGFGLFD
• Function: Plays an important role in the elongation step of protein synthesis.
• KEGG Pathway:
  Ribosome (hsa03010)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Peptide chain elongation (R-HSA-156902)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Viral mRNA Translation (R-HSA-192823)
  Selenocysteine synthesis (R-HSA-2408557)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Eukaryotic Translation Termination (R-HSA-72764)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Limited	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Large ribosomal subunit protein P1 (RPLP1) decreases the response to substance of Paclitaxel.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Large ribosomal subunit protein P1 (RPLP1).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Large ribosomal subunit protein P1 (RPLP1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Large ribosomal subunit protein P1 (RPLP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein P1 (RPLP1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein P1 (RPLP1).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Large ribosomal subunit protein P1 (RPLP1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein P1 (RPLP1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein P1 (RPLP1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Large ribosomal subunit protein P1 (RPLP1).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Large ribosomal subunit protein P1 (RPLP1).	[13]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Large ribosomal subunit protein P1 (RPLP1).	[14]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Large ribosomal subunit protein P1 (RPLP1).	[15]

References

• [1] Two new human cholangiocarcinoma cell lines and their cytogenetics and responses to growth factors, hormones, cytokines or immunologic effector cells.Int J Cancer. 1992 Sep 9;52(2):252-60. doi: 10.1002/ijc.2910520217.
• [2] Rplp1 bypasses replicative senescence and contributes to transformation.Exp Cell Res. 2009 May 1;315(8):1372-83. doi: 10.1016/j.yexcr.2009.02.007. Epub 2009 Feb 20.
• [3] RPLP1 promotes tumor metastasis and is associated with a poor prognosis in triple-negative breast cancer patients.Cancer Cell Int. 2018 Oct 25;18:170. doi: 10.1186/s12935-018-0658-0. eCollection 2018.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] 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.
• [10] 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.
• [11] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [14] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [15] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [16] cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance. Breast Cancer Res Treat. 2006 Mar;96(1):17-39. doi: 10.1007/s10549-005-9026-6. Epub 2005 Dec 2.