Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4TQZ9F)

• DOT Name: Regulatory-associated protein of mTOR (RPTOR)
• Synonyms: Raptor; p150 target of rapamycin (TOR)-scaffold protein
• Gene Name: RPTOR
• Related Disease:
  Progressive external ophthalmoplegia
  Bone disease
  Classic Hodgkin lymphoma
  Cleidocranial dysplasia 1
  Colorectal carcinoma
  Cystic fibrosis
  Dengue
  Esophageal squamous cell carcinoma
  Gastrointestinal mucositis
  Glioma
  Hepatitis C virus infection
  Hyperaldosteronism
  Hyperglycemia
  Male infertility
  Mitochondrial disease
  Neuralgia
  Nicotine dependence
  Obesity
  Osteoarthritis
  Plasma cell myeloma
  Retinal vein occlusion
  Triple negative breast cancer
  Ulcerative colitis
  Breast cancer
  Breast carcinoma
  High blood pressure
  Moyamoya disease
  Neurofibromatosis type 1
  Pancreatic cancer
  Tuberous sclerosis
  Acute myelogenous leukaemia
  Migraine disorder
• UniProt ID: RPTOR_HUMAN
• PDB ID: 5H64; 6BCU; 6BCX; 6SB0; 6SB2; 6U62; 7OWG; 7PEA; 7PEB; 7PEC; 7UX2; 7UXC; 7UXH; 8ERA
• Pfam ID: PF02985 ; PF14538 ; PF00400
• Sequence:
  MESEMLQSPLLGLGEEDEADLTDWNLPLAFMKKRHCEKIEGSKSLAQSWRMKDRMKTVSV
  ALVLCLNVGVDPPDVVKTTPCARLECWIDPLSMGPQKALETIGANLQKQYENWQPRARYK
  QSLDPTVDEVKKLCTSLRRNAKEERVLFHYNGHGVPRPTVNGEVWVFNKNYTQYIPLSIY
  DLQTWMGSPSIFVYDCSNAGLIVKSFKQFALQREQELEVAAINPNHPLAQMPLPPSMKNC
  IQLAACEATELLPMIPDLPADLFTSCLTTPIKIALRWFCMQKCVSLVPGVTLDLIEKIPG
  RLNDRRTPLGELNWIFTAITDTIAWNVLPRDLFQKLFRQDLLVASLFRNFLLAERIMRSY
  NCTPVSSPRLPPTYMHAMWQAWDLAVDICLSQLPTIIEEGTAFRHSPFFAEQLTAFQVWL
  TMGVENRNPPEQLPIVLQVLLSQVHRLRALDLLGRFLDLGPWAVSLALSVGIFPYVLKLL
  QSSARELRPLLVFIWAKILAVDSSCQADLVKDNGHKYFLSVLADPYMPAEHRTMTAFILA
  VIVNSYHTGQEACLQGNLIAICLEQLNDPHPLLRQWVAICLGRIWQNFDSARWCGVRDSA
  HEKLYSLLSDPIPEVRCAAVFALGTFVGNSAERTDHSTTIDHNVAMMLAQLVSDGSPMVR
  KELVVALSHLVVQYESNFCTVALQFIEEEKNYALPSPATTEGGSLTPVRDSPCTPRLRSV
  SSYGNIRAVATARSLNKSLQNLSLTEESGGAVAFSPGNLSTSSSASSTLGSPENEEHILS
  FETIDKMRRASSYSSLNSLIGVSFNSVYTQIWRVLLHLAADPYPEVSDVAMKVLNSIAYK
  ATVNARPQRVLDTSSLTQSAPASPTNKGVHIHQAGGSPPASSTSSSSLTNDVAKQPVSRD
  LPSGRPGTTGPAGAQYTPHSHQFPRTRKMFDKGPEQTADDADDAAGHKSFISATVQTGFC
  DWSARYFAQPVMKIPEEHDLESQIRKEREWRFLRNSRVRRQAQQVIQKGITRLDDQIFLN
  RNPGVPSVVKFHPFTPCIAVADKDSICFWDWEKGEKLDYFHNGNPRYTRVTAMEYLNGQD
  CSLLLTATDDGAIRVWKNFADLEKNPEMVTAWQGLSDMLPTTRGAGMVVDWEQETGLLMS
  SGDVRIVRIWDTDREMKVQDIPTGADSCVTSLSCDSHRSLIVAGLGDGSIRVYDRRMALS
  ECRVMTYREHTAWVVKASLQKRPDGHIVSVSVNGDVRIFDPRMPESVNVLQIVKGLTALD
  IHPQADLIACGSVNQFTAIYNSSGELINNIKYYDGFMGQRVGAISCLAFHPHWPHLAVGS
  NDYYISVYSVEKRVR
• Function: Component of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy. The mTORC1 complex is inhibited in response to starvation and amino acid depletion. Within the mTORC1 complex, RPTOR acts both as a molecular adapter, which (1) mediates recruitment of mTORC1 to lysosomal membranes via interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), and a (2) substrate-specific adapter, which promotes substrate specificity by binding to TOS motif-containing proteins and direct them towards the active site of the MTOR kinase domain for phosphorylation. mTORC1 complex regulates many cellular processes, such as odontoblast and osteoclast differentiation or neuronal transmission. mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD).
• Tissue Specificity: Highly expressed in skeletal muscle, and in a lesser extent in brain, lung, small intestine, kidney and placenta.; [Isoform 3]: Widely expressed, with highest levels in nasal mucosa and pituitary and lowest in spleen.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  Thermogenesis (hsa04714)
  Insulin sig.ling pathway (hsa04910)
  Shigellosis (hsa05131)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  MTOR signalling (R-HSA-165159)
  mTORC1-mediated signalling (R-HSA-166208)
  HSF1-dependent transactivation (R-HSA-3371571)
  Energy dependent regulation of mTOR by LKB1-AMPK (R-HSA-380972)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Amino acids regulate mTORC1 (R-HSA-9639288)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive external ophthalmoplegia	DISX4ATI	Definitive	Genetic Variation	[1]
Bone disease	DISE1F82	Strong	Biomarker	[2]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[3]
Cleidocranial dysplasia 1	DIS2OHLA	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[6]
Dengue	DISKH221	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[8]
Gastrointestinal mucositis	DIS140OB	Strong	Genetic Variation	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[11]
Hyperaldosteronism	DIS3WGAL	Strong	Altered Expression	[12]
Hyperglycemia	DIS0BZB5	Strong	Genetic Variation	[9]
Male infertility	DISY3YZZ	Strong	Biomarker	[13]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[14]
Neuralgia	DISWO58J	Strong	Biomarker	[15]
Nicotine dependence	DISZD9W7	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Genetic Variation	[17]
Osteoarthritis	DIS05URM	Strong	Biomarker	[18]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[2]
Retinal vein occlusion	DISSVWOE	Strong	Biomarker	[19]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[20]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[21]
Breast cancer	DIS7DPX1	moderate	Biomarker	[22]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[22]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[23]
Moyamoya disease	DISO62CA	moderate	Genetic Variation	[24]
Neurofibromatosis type 1	DIS53JH9	moderate	Genetic Variation	[25]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[26]
Tuberous sclerosis	DISEMUGZ	moderate	Posttranslational Modification	[27]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[28]
Migraine disorder	DISFCQTG	Limited	Altered Expression	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Regulatory-associated protein of mTOR (RPTOR) affects the response to substance of Nicotine.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Regulatory-associated protein of mTOR (RPTOR).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Regulatory-associated protein of mTOR (RPTOR).	[34]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Regulatory-associated protein of mTOR (RPTOR).	[38]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the phosphorylation of Regulatory-associated protein of mTOR (RPTOR).	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of Regulatory-associated protein of mTOR (RPTOR).	[40]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Regulatory-associated protein of mTOR (RPTOR).	[46]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Regulatory-associated protein of mTOR (RPTOR).	[46]
Orotic acid	DMP6BSH	Investigative	Orotic acid decreases the phosphorylation of Regulatory-associated protein of mTOR (RPTOR).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[33]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[35]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[36]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Regulatory-associated protein of mTOR (RPTOR).	[37]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Regulatory-associated protein of mTOR (RPTOR).	[41]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[42]
MLN4924	DMP36KD	Phase 3	MLN4924 increases the expression of Regulatory-associated protein of mTOR (RPTOR).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[45]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Regulatory-associated protein of mTOR (RPTOR).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[47]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Regulatory-associated protein of mTOR (RPTOR).	[48]

References

• [1] Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase gamma associated with progressive external ophthalmoplegia.Hum Mol Genet. 2006 Jan 15;15(2):363-74. doi: 10.1093/hmg/ddi454. Epub 2005 Dec 20.
• [2] New insights in myeloma-induced osteolysis.Leuk Lymphoma. 2003 Sep;44(9):1463-7. doi: 10.3109/10428190309178765.
• [3] The role of chemokines in Hodgkin's disease.Leuk Lymphoma. 2000 Jul;38(3-4):363-71. doi: 10.3109/10428190009087027.
• [4] mTOR/Raptor signaling is critical for skeletogenesis in mice through the regulation of Runx2 expression.Cell Death Differ. 2017 Nov;24(11):1886-1899. doi: 10.1038/cdd.2017.110. Epub 2017 Jul 7.
• [5] miR-496, miR-1185, miR-654, miR-3183 and miR-495 are downregulated in colorectal cancer cells and have putative roles in the mTOR pathway.Oncol Lett. 2019 Aug;18(2):1657-1668. doi: 10.3892/ol.2019.10508. Epub 2019 Jun 21.
• [6] RPTOR, a novel target of miR-155, elicits a fibrotic phenotype of cystic fibrosis lung epithelium by upregulating CTGF.RNA Biol. 2016 Sep;13(9):837-47. doi: 10.1080/15476286.2016.1197484. Epub 2016 Jun 10.
• [7] MIP-1 alpha and MIP-1 beta induction by dengue virus.J Med Virol. 2001 Oct;65(2):324-30. doi: 10.1002/jmv.2037.
• [8] Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations.J Thorac Oncol. 2013 Jun;8(6):788-95. doi: 10.1097/JTO.0b013e31828916c6.
• [9] Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer. PLoS One. 2017 Jul 20;12(7):e0180192.
• [10] Identification of expression quantitative trait loci of RPTOR for susceptibility to glioma.Tumour Biol. 2016 Feb;37(2):2305-11. doi: 10.1007/s13277-015-3956-3. Epub 2015 Sep 11.
• [11] Pretreatment serum macrophage inflammatory protein (MIP)-1 levels predict sustained virological responses to re-treatment in patients with chronic hepatitis C virus infection.Int J Infect Dis. 2015 Apr;33:15-21. doi: 10.1016/j.ijid.2014.08.021. Epub 2014 Oct 24.
• [12] Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.FASEB J. 2016 Jul;30(7):2511-27. doi: 10.1096/fj.201500042. Epub 2016 Mar 22.
• [13] Proteomic Profiling Analysis of Male Infertility in Spodoptera Litura Larvae Challenged with Azadirachtin and its Potential-Regulated Pathways in the Following Stages.Proteomics. 2018 Oct;18(19):e1800192. doi: 10.1002/pmic.201800192. Epub 2018 Sep 2.
• [14] mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae.Hum Mol Genet. 2010 Jun 1;19(11):2123-33. doi: 10.1093/hmg/ddq089. Epub 2010 Feb 25.
• [15] Involvement of Macrophage Inflammatory Protein-1 Family Members in the Development of Diabetic Neuropathy and Their Contribution to Effectiveness of Morphine.Front Immunol. 2018 Mar 12;9:494. doi: 10.3389/fimmu.2018.00494. eCollection 2018.
• [16] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [17] Seasonal effects of the UCP3 and the RPTOR gene polymorphisms on obesity traits in Japanese adults.J Physiol Anthropol. 2014 Dec 22;33(1):38. doi: 10.1186/1880-6805-33-38.
• [18] Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis.J Orthop Res. 2008 Jan;26(1):106-16. doi: 10.1002/jor.20486.
• [19] The anti-inflammatory and anti-oxidative effects of conbercept in treatment of macular edema secondary to retinal vein occlusion.Biochem Biophys Res Commun. 2019 Jan 22;508(4):1264-1270. doi: 10.1016/j.bbrc.2018.12.049. Epub 2018 Dec 15.
• [20] Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells.Int J Oncol. 2018 Mar;52(3):828-840. doi: 10.3892/ijo.2018.4244. Epub 2018 Jan 15.
• [21] Colonic epithelial mTORC1 promotes ulcerative colitis through COX-2-mediated Th17 responses.Mucosal Immunol. 2018 Nov;11(6):1663-1673. doi: 10.1038/s41385-018-0018-3. Epub 2018 Aug 6.
• [22] DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA.Oncotarget. 2016 Sep 27;7(39):64191-64202. doi: 10.18632/oncotarget.11640.
• [23] Interethnic analyses of blood pressure loci in populations of East Asian and European descent.Nat Commun. 2018 Nov 28;9(1):5052. doi: 10.1038/s41467-018-07345-0.
• [24] Novel Susceptibility Loci for Moyamoya Disease Revealed by a Genome-Wide Association Study.Stroke. 2018 Jan;49(1):11-18. doi: 10.1161/STROKEAHA.117.017430.
• [25] Subependymal giant cell astrocytoma-like astrocytoma: a neoplasm with a distinct phenotype and frequent neurofibromatosis type-1-association.Mod Pathol. 2018 Dec;31(12):1787-1800. doi: 10.1038/s41379-018-0103-x. Epub 2018 Jul 4.
• [26] Genetic variants in the liver kinase B1-AMP-activated protein kinase pathway genes and pancreatic cancer risk.Mol Carcinog. 2019 Aug;58(8):1338-1348. doi: 10.1002/mc.23018. Epub 2019 Apr 17.
• [27] Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis.Mol Cell Biol. 2006 Sep;26(17):6425-34. doi: 10.1128/MCB.01254-05.
• [28] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [29] Increased Serum CD14 Level Is Associated with Depletion of TNF- in Monocytes in Migraine Patients during Interictal Period.Int J Mol Sci. 2017 Feb 13;18(2):398. doi: 10.3390/ijms18020398.
• [30] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [31] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [32] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [33] 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.
• [34] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [35] 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.
• [36] The human myometrium differentially expresses mTOR signalling components before and during pregnancy: evidence for regulation by progesterone. J Steroid Biochem Mol Biol. 2014 Jan;139:166-72. doi: 10.1016/j.jsbmb.2013.02.017. Epub 2013 Mar 26.
• [37] 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.
• [38] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [39] Pioglitazone, a PPAR agonist, attenuates PDGF-induced vascular smooth muscle cell proliferation through AMPK-dependent and AMPK-independent inhibition of mTOR/p70S6K and ERK signaling. Biochem Pharmacol. 2016 Feb 1;101:54-70. doi: 10.1016/j.bcp.2015.11.026. Epub 2015 Nov 28.
• [40] Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells. Biochem Pharmacol. 2013 Jul 15;86(2):317-28. doi: 10.1016/j.bcp.2013.05.003. Epub 2013 May 13.
• [41] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [42] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [43] Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation. J Biol Chem. 2015 May 29;290(22):14120-9. doi: 10.1074/jbc.M114.633057. Epub 2015 Apr 20.
• [44] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [45] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [46] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [47] 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.
• [48] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [49] Proliferating effect of orotic acid through mTORC1 activation mediated by negative regulation of AMPK in SK-Hep1 hepatocellular carcinoma cells. J Toxicol Sci. 2012;37(4):813-21. doi: 10.2131/jts.37.813.
• [50] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.