Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZ3U85)

• DOT Name: Dual specificity protein phosphatase 22 (DUSP22)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; JNK-stimulatory phosphatase-1; JSP-1; Low molecular weight dual specificity phosphatase 2; LMW-DSP2; Mitogen-activated protein kinase phosphatase x; MAP kinase phosphatase x; MKP-x
• Gene Name: DUSP22
• Related Disease:
  Rheumatoid arthritis
  Advanced cancer
  Alzheimer disease
  Anaplastic large cell lymphoma
  Angioimmunoblastic T-cell Lymphoma
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cerebral palsy
  Colorectal carcinoma
  Hereditary spherocytosis type 1
  Inflammatory bowel disease
  Isolated cleft palate
  Lung cancer
  Lung carcinoma
  Lymphoma
  Lymphoproliferative syndrome
  Mycosis fungoides
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Prostate cancer
  Prostate carcinoma
  Skin cancer
  Systemic lupus erythematosus
  Obesity
  Alopecia
  Small lymphocytic lymphoma
• UniProt ID: DUS22_HUMAN
• PDB ID: 1WRM; 4WOH; 6L1S; 6LMY; 6LOT; 6LOU; 6LVQ; 7C8S
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MGNGMNKILPGLYIGNFKDARDAEQLSKNKVTHILSVHDSARPMLEGVKYLCIPAADSPS
  QNLTRHFKESIKFIHECRLRGESCLVHCLAGVSRSVTLVIAYIMTVTDFGWEDALHTVRA
  GRSCANPNVGFQRQLQEFEKHEVHQYRQWLKEEYGESPLQDAEEAKNILAAPGILKFWAF
  LRRL
• Function: Activates the Jnk signaling pathway.
• Tissue Specificity: Ubiquitous. Highest expression seen in heart, placenta, lung, liver, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Posttranslational Modification	[3]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Genetic Variation	[4]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Strong	Genetic Variation	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Hereditary spherocytosis type 1	DIS34V1Z	Strong	Altered Expression	[10]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[11]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Lymphoma	DISN6V4S	Strong	Biomarker	[12]
Lymphoproliferative syndrome	DISMVL8O	Strong	Biomarker	[13]
Mycosis fungoides	DIS62RB8	Strong	Genetic Variation	[14]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Genetic Variation	[15]
Prostate cancer	DISF190Y	Strong	Altered Expression	[16]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[16]
Skin cancer	DISTM18U	Strong	Biomarker	[10]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[17]
Obesity	DIS47Y1K	moderate	Biomarker	[18]
Alopecia	DIS37HU4	Limited	Genetic Variation	[19]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[20]

11 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 Dual specificity protein phosphatase 22 (DUSP22).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[22]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Dual specificity protein phosphatase 22 (DUSP22).	[23]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[24]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[22]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[22]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[22]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Dual specificity protein phosphatase 22 (DUSP22).	[27]

References

• [1] Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.Arthritis Rheumatol. 2018 Apr;70(4):528-536. doi: 10.1002/art.40408. Epub 2018 Feb 18.
• [2] Dysfunction of Poly (ADP-Ribose) Glycohydrolase Induces a Synthetic Lethal Effect in Dual Specificity Phosphatase 22-Deficient Lung Cancer Cells.Cancer Res. 2019 Aug 1;79(15):3851-3861. doi: 10.1158/0008-5472.CAN-18-1037. Epub 2019 May 29.
• [3] Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer's disease.Hippocampus. 2014 Apr;24(4):363-8. doi: 10.1002/hipo.22245. Epub 2014 Jan 28.
• [4] ALCL by any other name: the many facets of anaplastic large cell lymphoma.Pathology. 2020 Jan;52(1):100-110. doi: 10.1016/j.pathol.2019.09.007. Epub 2019 Nov 6.
• [5] Molecular Pathogenesis of Peripheral T Cell Lymphoma.Curr Hematol Malig Rep. 2015 Dec;10(4):429-37. doi: 10.1007/s11899-015-0289-7.
• [6] The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck.Nat Commun. 2014 Apr 9;5:3618. doi: 10.1038/ncomms4618.
• [7] DUSP22/LMW-DSP2 regulates estrogen receptor-alpha-mediated signaling through dephosphorylation of Ser-118.Oncogene. 2007 Sep 6;26(41):6038-49. doi: 10.1038/sj.onc.1210426. Epub 2007 Mar 26.
• [8] Genome-wide DNA methylation profiles according to Chlamydophila psittaci infection and the response to doxycycline treatment in ocular adnexal lymphoma.Mol Vis. 2014 Jul 19;20:1037-47. eCollection 2014.
• [9] Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients.Tumour Biol. 2015 Nov;36(11):8531-5. doi: 10.1007/s13277-015-3588-7. Epub 2015 Jun 2.
• [10] DUSP22 promotes senescence of HS-1 skin cancer cells through triggering MAPK signaling pathway.Eur Rev Med Pharmacol Sci. 2018 Nov;22(22):7819-7825. doi: 10.26355/eurrev_201811_16406.
• [11] JNK Pathway-Associated Phosphatase/DUSP22 Suppresses CD4(+) T-Cell Activation and Th1/Th17-Cell Differentiation and Negatively Correlates with Clinical Activity in Inflammatory Bowel Disease.Front Immunol. 2017 Jul 4;8:781. doi: 10.3389/fimmu.2017.00781. eCollection 2017.
• [12] Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay.Haematologica. 2020 Jun;105(6):1582-1592. doi: 10.3324/haematol.2019.226647. Epub 2019 Sep 5.
• [13] DUSP22-IRF4 rearrangement in AIDS-associated ALK-negative anaplastic large cell lymphoma.BMJ Case Rep. 2019 Sep 30;12(9):e230641. doi: 10.1136/bcr-2019-230641.
• [14] Mycosis fungoides in Taiwan shows a relatively high frequency of large cell transformation and CD56 expression.Pathology. 2018 Dec;50(7):718-724. doi: 10.1016/j.pathol.2018.08.008. Epub 2018 Oct 20.
• [15] Molecular alterations and tumor suppressive function of the DUSP22 (Dual Specificity Phosphatase 22) gene in peripheral T-cell lymphoma subtypes.Oncotarget. 2016 Oct 18;7(42):68734-68748. doi: 10.18632/oncotarget.11930.
• [16] DUSP22 suppresses prostate cancer proliferation by targeting the EGFR-AR axis.FASEB J. 2019 Dec;33(12):14653-14667. doi: 10.1096/fj.201802558RR. Epub 2019 Nov 5.
• [17] MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus.Cells. 2019 Nov 13;8(11):1433. doi: 10.3390/cells8111433.
• [18] Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression.Theranostics. 2019 May 26;9(12):3501-3514. doi: 10.7150/thno.31951. eCollection 2019.
• [19] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [20] Mutations in NOTCH1 PEST domain orchestrate CCL19-driven homing of chronic lymphocytic leukemia cells by modulating the tumor suppressor gene DUSP22.Leukemia. 2017 Sep;31(9):1882-1893. doi: 10.1038/leu.2016.383. Epub 2016 Dec 26.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [25] Hypomethylation of dual specificity phosphatase 22 promoter correlates with duration of service in firefighters and is inducible by low-dose benzo[a]pyrene. J Occup Environ Med. 2012 Jul;54(7):774-80. doi: 10.1097/JOM.0b013e31825296bc.
• [26] 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.
• [27] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.