Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1B19RU)

• DOT Name: E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)
• Synonyms: EC 2.3.2.26; EC 2.3.2.36; HECT-type E3 ubiquitin transferase NED4L; NEDD4.2; Nedd4-2
• Gene Name: NEDD4L
• Related Disease:
  Hyperglycemia
  Parkinson disease
  Periventricular nodular heterotopia 7
  Advanced cancer
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Cardiovascular disease
  Congestive heart failure
  Endometrial cancer
  Endometrial carcinoma
  Epilepsy
  Essential hypertension
  Glioma
  Heterotopia, periventricular, X-linked dominant
  High blood pressure
  Isolated cleft palate
  Lung cancer
  Lung carcinoma
  Mental disorder
  Metastatic malignant neoplasm
  Migraine disorder
  Migraine with aura
  Neoplasm
  Nephronophthisis 2
  Nephropathy
  Obesity
  Sezary syndrome
  Syndactyly
  Triple negative breast cancer
  Acute myelogenous leukaemia
  Asthma
  Melanoma
  Neurodevelopmental disorder
  Periventricular nodular heterotopia
  Endometriosis
  Gastric cancer
  Non-small-cell lung cancer
  Stomach cancer
  Cleft palate
  Gallbladder cancer
  Gallbladder carcinoma
  Hepatocellular carcinoma
  Paroxysmal nocturnal haemoglobinuria
• UniProt ID: NED4L_HUMAN
• PDB ID: 2LAJ; 2LB2; 2LTY; 2MPT; 2NSQ; 2ONI; 3JVZ; 3JW0; 5HPK; 6ZBT; 6ZC9; 7LP1; 7LP2; 7LP3; 7LP4; 7LP5; 7NMZ
• EC Number: 2.3.2.26; 2.3.2.36
• Pfam ID: PF00168 ; PF00632 ; PF00397
• Sequence:
  MATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELAL
  VQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDP
  TMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYMPKNGGQDEENSDQRDDMEHGWEVVDSN
  DSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRTTQWHRPSLMDVSSESDNNIRQI
  NQEAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETISEEVNIAGDSLGLALPPPPASPGS
  RTSPQELSEELSRRLQITPDSNGEQFSSLIQREPSSRLRSCSVTDAVAEQGHLPPPSAPA
  GRARSSTVTGGEEPTPSVAYVHTTPGLPSGWEERKDAKGRTYYVNHNNRTTTWTRPIMQL
  AEDGASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRRAVKDTLSNPQSP
  QPSPYNSPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKT
  SLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQWEDPRLQNPAITGPAVPYSREFKQK
  YDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDY
  GGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFTFIGRVAGLA
  VFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPTELDLMFCIDEE
  NFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLI
  KIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQ
  FVTGTSRVPMNGFAELYGSNGPQLFTIEQWGSPEKLPRAHTCFNRLDLPPYETFEDLREK
  LLMAVENAQGFEGVD
• Function: E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Plays a role in dendrite formation by melanocytes. Involved in the regulation of TOR signaling. Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF. Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3.
• Tissue Specificity: Ubiquitously expressed, with highest levels in prostate, pancreas, and kidney . Expressed in melanocytes .
• KEGG Pathway:
  Ubiquitin mediated proteolysis (hsa04120)
  Endocytosis (hsa04144)
  Tight junction (hsa04530)
  Aldosterone-regulated sodium reabsorption (hsa04960)
• Reactome Pathway:
  Downregulation of TGF-beta receptor signaling (R-HSA-2173788)
  Downregulation of SMAD2/3 (R-HSA-2173795)
  Stimuli-sensing channels (R-HSA-2672351)
  Antigen processing (R-HSA-983168)
  Budding and maturation of HIV virion (R-HSA-162588)
• BioCyc Pathway: MetaCyc:ENSG00000049759-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[1]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[2]
Periventricular nodular heterotopia 7	DIS1E2VZ	Definitive	Autosomal dominant	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[8]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[8]
Epilepsy	DISBB28L	Strong	Biomarker	[9]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Heterotopia, periventricular, X-linked dominant	DISP6LBO	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[13]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[14]
Lung cancer	DISCM4YA	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[15]
Mental disorder	DIS3J5R8	Strong	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[17]
Migraine with aura	DISDM7I8	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Nephronophthisis 2	DIS5Y5KV	Strong	Biomarker	[18]
Nephropathy	DISXWP4P	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Genetic Variation	[20]
Sezary syndrome	DISFMTC7	Strong	Altered Expression	[21]
Syndactyly	DISZK2BT	Strong	Biomarker	[12]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[6]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[22]
Asthma	DISW9QNS	moderate	Genetic Variation	[23]
Melanoma	DIS1RRCY	moderate	Biomarker	[24]
Neurodevelopmental disorder	DIS372XH	moderate	Genetic Variation	[25]
Periventricular nodular heterotopia	DISU3ZRI	Supportive	Autosomal dominant	[12]
Endometriosis	DISX1AG8	Disputed	Biomarker	[26]
Gastric cancer	DISXGOUK	Disputed	Altered Expression	[27]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Altered Expression	[16]
Stomach cancer	DISKIJSX	Disputed	Altered Expression	[27]
Cleft palate	DIS6G5TF	Limited	Genetic Variation	[14]
Gallbladder cancer	DISXJUAF	Limited	Altered Expression	[28]
Gallbladder carcinoma	DISD6ACL	Limited	Altered Expression	[28]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[29]
Paroxysmal nocturnal haemoglobinuria	DISBHMYH	Limited	Genetic Variation	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) increases the Insomnia ADR of Chlorothiazide.	[52]

20 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 E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[37]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[39]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[40]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[41]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[42]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[43]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[45]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[46]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[50]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[51]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[47]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L).	[47]

References

• [1] O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.Int J Cardiol. 2018 Jun 1;260:74-81. doi: 10.1016/j.ijcard.2018.02.099. Epub 2018 Feb 27.
• [2] Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model.Cell Death Dis. 2017 Feb 2;8(2):e2574. doi: 10.1038/cddis.2016.454.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Genetic variation in NEDD4L, an epithelial sodium channel regulator, is associated with cardiovascular disease and cardiovascular death.J Hypertens. 2014 Feb;32(2):294-9. doi: 10.1097/HJH.0000000000000044.
• [5] Differentially expressed tRFs in CD5 positive relapsed & refractory diffuse large B cell lymphoma and the bioinformatic analysis for their potential clinical use.Biol Direct. 2019 Nov 27;14(1):23. doi: 10.1186/s13062-019-0255-8.
• [6] The miR-106b-25 cluster mediates breast tumor initiation through activation of NOTCH1 via direct repression of NEDD4L.Oncogene. 2018 Jul;37(28):3879-3893. doi: 10.1038/s41388-018-0239-7. Epub 2018 Apr 17.
• [7] Calcium-dependent Nedd4-2 upregulation mediates degradation of the cardiac sodium channel Nav1.5: implications for heart failure.Acta Physiol (Oxf). 2017 Sep;221(1):44-58. doi: 10.1111/apha.12872. Epub 2017 Apr 6.
• [8] Neural precursor cell-expressed developmentally down-regulated 4-like: a new biomarker in the pathophysiology of endometrial cancer.J Int Med Res. 2018 Sep;46(9):3709-3716. doi: 10.1177/0300060518777944. Epub 2018 Jul 12.
• [9] PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination.Cell Death Dis. 2019 Jul 18;10(8):545. doi: 10.1038/s41419-019-1781-0.
• [10] Gender difference in association of NEDD4L gene variants among southern Han Chinese with essential hypertension - a population-based case-control study.Clin Exp Hypertens. 2014;36(5):309-14. doi: 10.3109/10641963.2013.827693. Epub 2013 Sep 18.
• [11] IGF-1-enhanced miR-513a-5p signaling desensitizes glioma cells totemozolomideby targeting the NEDD4L-inhibited Wnt/-cateninpathway.PLoS One. 2019 Dec 5;14(12):e0225913. doi: 10.1371/journal.pone.0225913. eCollection 2019.
• [12] Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nat Genet. 2016 Nov;48(11):1349-1358. doi: 10.1038/ng.3676. Epub 2016 Oct 3.
• [13] Deletion of Nedd4-2 results in progressive kidney disease in mice.Cell Death Differ. 2017 Dec;24(12):2150-2160. doi: 10.1038/cdd.2017.137. Epub 2017 Sep 1.
• [14] Author Correction: A missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria, and cleft palate.J Hum Genet. 2019 Jul;64(7):701-702. doi: 10.1038/s10038-019-0610-8.
• [15] miR-93 promotes TGF--induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells.Tumour Biol. 2016 Apr;37(4):5645-51. doi: 10.1007/s13277-015-4328-8. Epub 2015 Nov 18.
• [16] Decreased expression of NEDD4L contributes to NSCLC progression and metastasis.Biochem Biophys Res Commun. 2019 May 28;513(2):398-404. doi: 10.1016/j.bbrc.2019.04.001. Epub 2019 Apr 6.
• [17] Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
• [18] Loss of inversin decreases transepithelial sodium transport in murine renal cells.Am J Physiol Cell Physiol. 2017 Dec 1;313(6):C664-C673. doi: 10.1152/ajpcell.00359.2016. Epub 2017 Oct 4.
• [19] Dietary sodium modulates nephropathy in Nedd4-2-deficient mice.Cell Death Differ. 2020 Jun;27(6):1832-1843. doi: 10.1038/s41418-019-0468-5. Epub 2019 Dec 4.
• [20] The impacts of the interaction of genetic variation, CYP112 and NEDD4L, with sodium intake on pediatric obesity with gender difference: a 3-year panel study.Int J Obes (Lond). 2017 Apr;41(4):542-550. doi: 10.1038/ijo.2016.232. Epub 2016 Dec 26.
• [21] Szary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3.Leukemia. 2008 Feb;22(2):393-9. doi: 10.1038/sj.leu.2405044. Epub 2007 Nov 22.
• [22] 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.
• [23] Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma.PLoS One. 2014 Aug 12;9(8):e104396. doi: 10.1371/journal.pone.0104396. eCollection 2014.
• [24] Pathobiological properties of the ubiquitin ligase Nedd4L in melanoma.Int J Exp Pathol. 2014 Feb;95(1):24-8. doi: 10.1111/iep.12051. Epub 2013 Oct 31.
• [25] A novel missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria and cleft palate.J Hum Genet. 2017 Sep;62(9):861-863. doi: 10.1038/jhg.2017.53. Epub 2017 May 18.
• [26] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [27] The correlation between NEDD4L and HIF-1 levels as a gastric cancer prognostic marker.Int J Med Sci. 2019 Oct 21;16(11):1517-1524. doi: 10.7150/ijms.34646. eCollection 2019.
• [28] Nedd4L modulates the transcription of metalloproteinase-1 and -13 genes to increase the invasive activity of gallbladder cancer.Int J Exp Pathol. 2011 Apr;92(2):79-86. doi: 10.1111/j.1365-2613.2010.00740.x. Epub 2010 Oct 5.
• [29] Downregulation of Nedd4L predicts poor prognosis, promotes tumor growth and inhibits MAPK/ERK signal pathway in hepatocellular carcinoma.Biochem Biophys Res Commun. 2018 Jan 1;495(1):1136-1143. doi: 10.1016/j.bbrc.2017.11.139. Epub 2017 Nov 22.
• [30] Multiple genomic copy number variants associated with periventricular nodular heterotopia indicate extreme genetic heterogeneity.Eur J Hum Genet. 2019 Jun;27(6):909-918. doi: 10.1038/s41431-019-0335-3. Epub 2019 Jan 25.
• [31] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [32] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [33] 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.
• [34] 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.
• [35] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [36] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [37] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [38] 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.
• [39] 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.
• [40] Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol Cancer Ther. 2007 Jan;6(1):51-60. doi: 10.1158/1535-7163.MCT-06-0144. Epub 2007 Jan 11.
• [41] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [42] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [43] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [44] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [45] 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.
• [46] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [47] 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.
• [48] Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
• [49] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [50] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [51] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [52] A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for a common variant in the adenosine receptor. Sleep. 2012 Jul 1;35(7):967-75. doi: 10.5665/sleep.1962.