Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYG179K)

• DOT Name: Protein phosphatase 1 regulatory subunit 15A (PPP1R15A)
• Synonyms: Growth arrest and DNA damage-inducible protein GADD34; Myeloid differentiation primary response protein MyD116 homolog
• Gene Name: PPP1R15A
• Related Disease:
  Motor neurone disease
  Stroke
  Adult glioblastoma
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Cardiac arrest
  Coronary atherosclerosis
  Fatty liver disease
  Glioblastoma multiforme
  Hepatitis C virus infection
  Herpes simplex infection
  IgA nephropathy
  Lymphoma
  Malignant pleural mesothelioma
  Medulloblastoma
  Melanoma
  Myocardial ischemia
  Neoplasm
  Obesity
  Parkinson disease
  Pediatric lymphoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Chronic obstructive pulmonary disease
  Colitis
  Neuroblastoma
  Tuberous sclerosis
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Rheumatoid arthritis
  Amyotrophic lateral sclerosis
  B-cell neoplasm
  Keratoconjunctivitis sicca
  Myasthenia gravis
  Nervous system inflammation
  Obstructive jaundice
• UniProt ID: PR15A_HUMAN
• PDB ID: 4XPN; 7NXV; 7NZM
• Pfam ID: PF10488
• Sequence:
  MAPGQAPHQATPWRDAHPFFLLSPVMGLLSRAWSRLRGLGPLEPWLVEAVKGAALVEAGL
  EGEARTPLAIPHTPWGRRPEEEAEDSGGPGEDRETLGLKTSSSLPEAWGLLDDDDGMYGE
  REATSVPRGQGSQFADGQRAPLSPSLLIRTLQGSDKNPGEEKAEEEGVAEEEGVNKFSYP
  PSHRECCPAVEEEDDEEAVKKEAHRTSTSALSPGSKPSTWVSCPGEEENQATEDKRTERS
  KGARKTSVSPRSSGSDPRSWEYRSGEASEEKEEKAHKETGKGEAAPGPQSSAPAQRPQLK
  SWWCQPSDEEEGEVKALGAAEKDGEAECPPCIPPPSAFLKAWVYWPGEDTEEEEDEEEDE
  DSDSGSDEEEGEAEASSSTPATGVFLKSWVYQPGEDTEEEEDEDSDTGSAEDEREAETSA
  STPPASAFLKAWVYRPGEDTEEEEDEDVDSEDKEDDSEAALGEAESDPHPSHPDQRAHFR
  GWGYRPGKETEEEEAAEDWGEAEPCPFRVAIYVPGEKPPPPWAPPRLPLRLQRRLKRPET
  PTHDPDPETPLKARKVRFSEKVTVHFLAVWAGPAQAARQGPWEQLARDRSRFARRITQAQ
  EELSPCLTPAARARAWARLRNPPLAPIPALTQTLPSSSVPSSPVQTTPLSQAVATPSRSS
  AAAAAALDLSGRRG
• Function: Recruits the serine/threonine-protein phosphatase PPP1CA to prevents excessive phosphorylation of the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing p53/TP53 phosphorylation on 'Ser-15'. Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux. Acts also a viral restriction factor by attenuating HIV-1 replication. Mechanistically, mediates the inhibition of HIV-1 TAR RNA-mediated translation ; (Microbial infection) Promotes enterovirus 71 replication by mediating the internal ribosome entry site (IRES) activity of viral 5'-UTR.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Response of EIF2AK1 (HRI) to heme deficiency (R-HSA-9648895)
  Downregulation of TGF-beta receptor signaling (R-HSA-2173788)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Motor neurone disease	DISUHWUI	Definitive	Biomarker	[1]
Stroke	DISX6UHX	Definitive	Therapeutic	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Cardiac arrest	DIS9DIA4	Strong	Altered Expression	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[7]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[8]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[9]
IgA nephropathy	DISZ8MTK	Strong	Altered Expression	[10]
Lymphoma	DISN6V4S	Strong	Biomarker	[4]
Malignant pleural mesothelioma	DIST2R60	Strong	Biomarker	[9]
Medulloblastoma	DISZD2ZL	Strong	Genetic Variation	[11]
Melanoma	DIS1RRCY	Strong	Biomarker	[12]
Myocardial ischemia	DISFTVXF	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[13]
Obesity	DIS47Y1K	Strong	Biomarker	[14]
Parkinson disease	DISQVHKL	Strong	Biomarker	[15]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[4]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[16]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[16]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[16]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[17]
Colitis	DISAF7DD	moderate	Biomarker	[18]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[19]
Tuberous sclerosis	DISEMUGZ	moderate	Genetic Variation	[20]
Epithelial ovarian cancer	DIS56MH2	Disputed	Biomarker	[21]
Ovarian cancer	DISZJHAP	Disputed	Biomarker	[21]
Ovarian neoplasm	DISEAFTY	Disputed	Biomarker	[21]
Rheumatoid arthritis	DISTSB4J	Disputed	Altered Expression	[22]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[23]
B-cell neoplasm	DISVY326	Limited	Biomarker	[24]
Keratoconjunctivitis sicca	DISNOENH	Limited	Biomarker	[25]
Myasthenia gravis	DISELRCI	Limited	Altered Expression	[26]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[27]
Obstructive jaundice	DIS2FDOT	Limited	Altered Expression	[24]

1 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 Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[33]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[34]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[38]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[40]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[41]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[42]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[43]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[44]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[45]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[46]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[47]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[48]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[49]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[50]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[51]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[52]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[53]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[54]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[55]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[39]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[56]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[57]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[58]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[59]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[58]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[58]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[58]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[60]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[61]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[62]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[63]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[64]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[65]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[66]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[67]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[34]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[68]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[69]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[70]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[71]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[71]
5-(N,N-hexamethylene)-amiloride	DMC4IUQ	Preclinical	5-(N,N-hexamethylene)-amiloride increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[72]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[73]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[74]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[75]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[76]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[77]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[78]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[79]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[80]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[81]
PATULIN	DM0RV9C	Investigative	PATULIN increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[82]
L-Serine	DM6WPIS	Investigative	L-Serine decreases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[83]
NMS-873	DMYKZ6U	Investigative	NMS-873 increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[84]
All-trans-retinal	DM6CEVB	Investigative	All-trans-retinal increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[85]
Fenthion	DMKEG49	Investigative	Fenthion increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[86]
A192621	DMV8AH6	Investigative	A192621 increases the expression of Protein phosphatase 1 regulatory subunit 15A (PPP1R15A).	[87]

References

• [1] The UPR-PERK pathway is not a promising therapeutic target for mutant SOD1-induced ALS.Neurobiol Dis. 2019 Jul;127:527-544. doi: 10.1016/j.nbd.2019.03.024. Epub 2019 Mar 26.
• [2] Mode of action of S-methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO) as a novel therapy for stroke in a rat model.Mol Neurobiol. 2014 Oct;50(2):655-72. doi: 10.1007/s12035-014-8658-0. Epub 2014 Feb 28.
• [3] Toxicity and Efficacy of a Novel GADD34-expressing Oncolytic HSV-1 for the Treatment of Experimental Glioblastoma.Clin Cancer Res. 2018 Jun 1;24(11):2574-2584. doi: 10.1158/1078-0432.CCR-17-2954. Epub 2018 Mar 6.
• [4] Female GADD34 mice develop age-related inflammation and hepatocellular carcinoma.Geriatr Gerontol Int. 2017 Dec;17(12):2593-2601. doi: 10.1111/ggi.13080. Epub 2017 Jun 21.
• [5] In vivo molecular mediators of cancer growth suppression and apoptosis by selenium in mammary and prostate models: lack of involvement of gadd genes.Mol Cancer Ther. 2009 Mar;8(3):682-91. doi: 10.1158/1535-7163.MCT-08-0908. Epub 2009 Mar 10.
• [6] Decreased levels of PDI and P5 in oligodendrocytes in Alzheimer's disease.Neuropathology. 2017 Dec;37(6):495-501. doi: 10.1111/neup.12395. Epub 2017 Jul 21.
• [7] Identification of the growth arrest and DNA damage protein GADD34 in the normal human heart and demonstration of alterations in expression following myocardial ischaemia.Int J Cardiol. 2006 Feb 8;107(1):126-9. doi: 10.1016/j.ijcard.2005.01.051.
• [8] No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection.J Gastroenterol Hepatol. 2011 Feb;26(2):319-27. doi: 10.1111/j.1440-1746.2010.06368.x.
• [9] Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma.Cancer Biol Ther. 2006 Jan;5(1):48-53. doi: 10.4161/cbt.5.1.2237. Epub 2006 Jan 12.
• [10] Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2 Phosphorylation.Cell Physiol Biochem. 2018;50(6):2203-2215. doi: 10.1159/000495061. Epub 2018 Nov 9.
• [11] Dual role of the integrated stress response in medulloblastoma tumorigenesis.Oncotarget. 2016 Sep 27;7(39):64124-64135. doi: 10.18632/oncotarget.11873.
• [12] GADD153 is an independent prognostic factor in melanoma: immunohistochemical and molecular genetic analysis.Histol Histopathol. 2002;17(3):805-11. doi: 10.14670/HH-17.805.
• [13] Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer.J Cancer Res Clin Oncol. 2016 Aug;142(8):1705-14. doi: 10.1007/s00432-016-2177-5. Epub 2016 May 13.
• [14] Integrated stress response activation by sleep fragmentation during late gestation in mice leads to emergence of adverse metabolic phenotype in offspring.Metabolism. 2017 Apr;69:188-198. doi: 10.1016/j.metabol.2017.01.026. Epub 2017 Jan 21.
• [15] Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.Exp Neurol. 2018 May;303:95-107. doi: 10.1016/j.expneurol.2018.01.015. Epub 2018 Feb 9.
• [16] Selenium decreases thyroid cancer cell growth by increasing expression of GADD153 and GADD34.Nutr Cancer. 2010;62(1):66-73. doi: 10.1080/01635580903191569.
• [17] Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae.Respir Res. 2017 Jan 28;18(1):27. doi: 10.1186/s12931-017-0510-4.
• [18] Combined NADPH oxidase 1 and interleukin 10 deficiency induces chronic endoplasmic reticulum stress and causes ulcerative colitis-like disease in mice.PLoS One. 2014 Jul 9;9(7):e101669. doi: 10.1371/journal.pone.0101669. eCollection 2014.
• [19] Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells.Free Radic Biol Med. 2001 Jan 15;30(2):213-21. doi: 10.1016/s0891-5849(00)00461-5.
• [20] GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress.Int J Mol Med. 2007 Mar;19(3):475-83.
• [21] The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis.Mol Cancer. 2014 Aug 12;13:189. doi: 10.1186/1476-4598-13-189.
• [22] Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies.Autoimmunity. 2016;49(3):172-8. doi: 10.3109/08916934.2016.1138220. Epub 2016 Feb 1.
• [23] Increased GADD34 in oligodendrocytes in Alzheimer's disease.Neurosci Lett. 2015 Aug 18;602:50-5. doi: 10.1016/j.neulet.2015.06.052. Epub 2015 Jul 2.
• [24] Yinchenhao decoction attenuates obstructive jaundice-induced liver injury and hepatocyte apoptosis by suppressing protein kinase RNA-like endoplasmic reticulum kinase-induced pathway.World J Gastroenterol. 2019 Nov 7;25(41):6205-6221. doi: 10.3748/wjg.v25.i41.6205.
• [25] GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress in Human Corneal Cells.Cell Rep. 2017 Dec 5;21(10):2895-2910. doi: 10.1016/j.celrep.2017.11.027.
• [26] A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients.Immunobiology. 2016 Nov;221(11):1227-36. doi: 10.1016/j.imbio.2016.06.012. Epub 2016 Jun 15.
• [27] Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis.Brain. 2019 Feb 1;142(2):344-361. doi: 10.1093/brain/awy322.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] Exploring pradimicin-IRD antineoplastic mechanisms and related DNA repair pathways. Chem Biol Interact. 2023 Feb 1;371:110342. doi: 10.1016/j.cbi.2023.110342. Epub 2023 Jan 10.
• [32] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [33] 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.
• [34] Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
• [35] 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.
• [36] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [37] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [38] Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions. BMC Genomics. 2008 Aug 7;9:376.
• [39] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [40] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [41] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [42] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [43] 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.
• [44] 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.
• [45] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [46] 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.
• [47] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [48] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [49] 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.
• [50] Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
• [51] Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol Cell Biol. 2004 Nov;24(22):9695-704. doi: 10.1128/MCB.24.22.9695-9704.2004.
• [52] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [53] 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.
• [54] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [55] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [56] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [57] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [58] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [59] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [60] Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells. Lipids Health Dis. 2010 Jun 2;9:56. doi: 10.1186/1476-511X-9-56.
• [61] The kinase inhibitor sorafenib induces cell death through a process involving induction of endoplasmic reticulum stress. Mol Cell Biol. 2007 Aug;27(15):5499-513. doi: 10.1128/MCB.01080-06. Epub 2007 Jun 4.
• [62] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [63] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [64] Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
• [65] Impact of epigallocatechin gallate on gene expression profiles of human hepatocellular carcinoma cell lines BEL7404/ADM and BEL7402/5-FU. Ai Zheng. 2008 Oct;27(10):1056-64.
• [66] Regulation of endoplasmic reticulum stress-induced cell death by ATF4 in neuroectodermal tumor cells. J Biol Chem. 2010 Feb 26;285(9):6091-100. doi: 10.1074/jbc.M109.014092. Epub 2009 Dec 18.
• [67] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [68] Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells. EMBO J. 2019 Jun 17;38(12):e101107. doi: 10.15252/embj.2018101107. Epub 2019 May 8.
• [69] 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.
• [70] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [71] Protective effect against Parkinson's disease-related insults through the activation of XBP1. Brain Res. 2009 Feb 27;1257:16-24. doi: 10.1016/j.brainres.2008.11.104. Epub 2008 Dec 16.
• [72] Amiloride derivatives induce apoptosis by depleting ER Ca(2+) stores in vascular endothelial cells. Br J Pharmacol. 2009 Apr;156(8):1296-304.
• [73] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [74] Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect. 2007 Oct;115(10):1460-6. doi: 10.1289/ehp.10180.
• [75] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [76] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [77] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [78] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [79] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
• [80] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
• [81] Chronic oxidative stress promotes GADD34-mediated phosphorylation of the TAR DNA-binding protein TDP-43, a modification linked to neurodegeneration. J Biol Chem. 2018 Jan 5;293(1):163-176. doi: 10.1074/jbc.M117.814111. Epub 2017 Nov 6.
• [82] Complementary cell-based high-throughput screens identify novel modulators of the unfolded protein response. J Biomol Screen. 2011 Sep;16(8):825-35. doi: 10.1177/1087057111414893. Epub 2011 Aug 15.
• [83] Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation. Neurotox Res. 2018 Jan;33(1):123-132. doi: 10.1007/s12640-017-9829-3. Epub 2017 Nov 2.
• [84] Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death. Nat Chem Biol. 2013 Sep;9(9):548-56. doi: 10.1038/nchembio.1313. Epub 2013 Jul 28.
• [85] Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration. Toxicol Sci. 2015 Jan;143(1):196-208. doi: 10.1093/toxsci/kfu223. Epub 2014 Oct 20.
• [86] Fenthion and terbufos induce DNA damage, the expression of tumor-related genes, and apoptosis in HEPG2 cells. Environ Mol Mutagen. 2011 Aug;52(7):529-37. doi: 10.1002/em.20652. Epub 2011 Apr 27.
• [87] Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor. BMC Cancer. 2008 Nov 28;8:354. doi: 10.1186/1471-2407-8-354.