Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHOU68T)

• DOT Name: Polycomb group RING finger protein 1 (PCGF1)
• Synonyms: Nervous system Polycomb-1; NSPc1; RING finger protein 68
• Gene Name: PCGF1
• Related Disease:
  Advanced cancer
  Glioma
  Malignant glioma
  Adult glioblastoma
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: PCGF1_HUMAN
• PDB ID: 4HPL; 4HPM; 5JH5; 8HCU
• Pfam ID: PF16207 ; PF13923
• Sequence:
  MASPQGGQIAIAMRLRNQLQSVYKMDPLRNEEEVRVKIKDLNEHIVCCLCAGYFVDATTI
  TECLHTFCKSCIVKYLQTSKYCPMCNIKIHETQPLLNLKLDRVMQDIVYKLVPGLQDSEE
  KRIREFYQSRGLDRVTQPTGEEPALSNLGLPFSSFDHSKAHYYRYDEQLNLCLERLSSGK
  DKNKSVLQNKYVRCSVRAEVRHLRRVLCHRLMLNPQHVQLLFDNEVLPDHMTMKQIWLSR
  WFGKPSPLLLQYSVKEKRR
• Function: Component of the Polycomb group (PcG) multiprotein BCOR complex, a complex required to maintain the transcriptionally repressive state of some genes, such as BCL6 and the cyclin-dependent kinase inhibitor, CDKN1A. Transcriptional repressor that may be targeted to the DNA by BCL6; this transcription repressor activity may be related to PKC signaling pathway. Represses CDKN1A expression by binding to its promoter, and this repression is dependent on the retinoic acid response element (RARE element). Promotes cell cycle progression and enhances cell proliferation as well. May have a positive role in tumor cell growth by down-regulating CDKN1A. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity. Regulates the expression of DPPA4 and NANOG in the NT2 embryonic carcinoma cells.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Polycomb repressive complex (hsa03083)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Malignant glioma	DISFXKOV	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Disputed	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[3]
Neoplasm	DISZKGEW	Disputed	Biomarker	[4]

11 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 Polycomb group RING finger protein 1 (PCGF1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polycomb group RING finger protein 1 (PCGF1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Polycomb group RING finger protein 1 (PCGF1).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Polycomb group RING finger protein 1 (PCGF1).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Polycomb group RING finger protein 1 (PCGF1).	[15]

References

• [1] NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of all-trans retinoic acid via targeting RDH16 in malignant glioma.Oncogene. 2017 Aug 17;36(33):4706-4718. doi: 10.1038/onc.2017.34. Epub 2017 Apr 10.
• [2] NSPc1 polycomb protein complex binds and crosstalks to lncRNAs in glioma H4 cells.Oncol Rep. 2019 Apr;41(4):2575-2584. doi: 10.3892/or.2019.7000. Epub 2019 Feb 5.
• [3] lncRNAs combine and crosstalk with NSPc1 in ATRA-induced differentiation of U87 glioma cells.Oncol Lett. 2019 Jun;17(6):5821-5829. doi: 10.3892/ol.2019.10254. Epub 2019 Apr 15.
• [4] NSPc1 is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the RARE element.Nucleic Acids Res. 2006;34(21):6158-69. doi: 10.1093/nar/gkl834. Epub 2006 Nov 6.
• [5] 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.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.