Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT14OQ1C)

• DOT Name: Protein lin-52 homolog (LIN52)
• Gene Name: LIN52
• Related Disease: Hepatocellular carcinoma
• UniProt ID: LIN52_HUMAN
• PDB ID: 4YOO; 6C48
• Pfam ID: PF10044
• Sequence:
  MGWKMASPTDGTDLEASLLSFEKLDRASPDLWPEQLPGVAEFAASFKSPITSSPPKWMAE
  IERDDIDMLKELGSLTTANLMEKVRGLQNLAYQLGLDESREMTRGKFLNILEKPKK
• KEGG Pathway: Cellular senescence (hsa04218)
• Reactome Pathway:
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  G0 and Early G1 (R-HSA-1538133)
  Polo-like kinase mediated events (R-HSA-156711)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A (R-HSA-69656)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[1]

8 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 Protein lin-52 homolog (LIN52).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein lin-52 homolog (LIN52).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein lin-52 homolog (LIN52).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein lin-52 homolog (LIN52).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein lin-52 homolog (LIN52).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein lin-52 homolog (LIN52).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein lin-52 homolog (LIN52).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein lin-52 homolog (LIN52).	[9]

References

• [1] High MYBL2 expression and transcription regulatory activity is associated with poor overall survival in patients with hepatocellular carcinoma.Curr Res Transl Med. 2018 Mar;66(1):27-32. doi: 10.1016/j.retram.2017.11.002. Epub 2017 Dec 21.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.