Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIL349E)

• DOT Name: Death effector domain-containing protein (DEDD)
• Synonyms: DEDPro1; Death effector domain-containing testicular molecule; FLDED-1
• Gene Name: DEDD
• Related Disease:
  Bladder cancer
  Classic Hodgkin lymphoma
  Lung adenocarcinoma
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Carcinoma
  Colon cancer
  Gastric cancer
  Neoplasm
  Stomach cancer
  Transitional cell carcinoma
  Urothelial carcinoma
• UniProt ID: DEDD_HUMAN
• Pfam ID: PF01335 ; PF20694
• Sequence:
  MAGLKRRASQVWPEEHGEQEHGLYSLHRMFDIVGTHLTHRDVRVLSFLFVDVIDDHERGL
  IRNGRDFLLALERQGRCDESNFRQVLQLLRIITRHDLLPYVTLKRRRAVCPDLVDKYLEE
  TSIRYVTPRALSDPEPRPPQPSKTVPPHYPVVCCPTSGPQMCSKRPARGRATLGSQRKRR
  KSVTPDPKEKQTCDIRLRVRAEYCQHETALQGNVFSNKQDPLERQFERFNQANTILKSRD
  LGSIICDIKFSELTYLDAFWRDYINGSLLEALKGVFITDSLKQAVGHEAIKLLVNVDEED
  YELGRQKLLRNLMLQALP
• Function: A scaffold protein that directs CASP3 to certain substrates and facilitates their ordered degradation during apoptosis. May also play a role in mediating CASP3 cleavage of KRT18. Regulates degradation of intermediate filaments during apoptosis. May play a role in the general transcription machinery in the nucleus and might be an important regulator of the activity of GTF3C3. Inhibits DNA transcription in vitro.
• Tissue Specificity: Widely expressed with highest levels in testis.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[4]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[5]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[6]
Carcinoma	DISH9F1N	moderate	Biomarker	[7]
Colon cancer	DISVC52G	moderate	Biomarker	[6]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[8]
Neoplasm	DISZKGEW	moderate	Biomarker	[8]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[8]
Transitional cell carcinoma	DISWVVDR	moderate	Biomarker	[7]
Urothelial carcinoma	DISRTNTN	moderate	Biomarker	[7]

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 Death effector domain-containing protein (DEDD).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Death effector domain-containing protein (DEDD).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Death effector domain-containing protein (DEDD).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Death effector domain-containing protein (DEDD).	[12]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Death effector domain-containing protein (DEDD).	[13]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Death effector domain-containing protein (DEDD).	[14]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Death effector domain-containing protein (DEDD).	[15]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Death effector domain-containing protein (DEDD).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Death effector domain-containing protein (DEDD).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Death effector domain-containing protein (DEDD).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Death effector domain-containing protein (DEDD).	[17]

References

• [1] miR-24-3p regulates bladder cancer cell proliferation, migration, invasion and autophagy by targeting DEDD.Oncol Rep. 2017 Feb;37(2):1123-1131. doi: 10.3892/or.2016.5326. Epub 2016 Dec 16.
• [2] MicroRNA-24-3p regulates Hodgkin's lymphoma cell proliferation, migration and invasion by targeting DEDD.Oncol Lett. 2019 Jan;17(1):365-371. doi: 10.3892/ol.2018.9599. Epub 2018 Oct 19.
• [3] Long Noncoding RNA LINC00472 Inhibits Proliferation and Promotes Apoptosis of Lung Adenocarcinoma Cells via Regulating miR-24-3p/ DEDD.Technol Cancer Res Treat. 2018 Jan 1;17:1533033818790490. doi: 10.1177/1533033818790490.
• [4] Changes in apoptotic gene expression in lymphocytes from rheumatoid arthritis and systemic lupus erythematosus patients compared with healthy lymphocytes.J Clin Immunol. 2010 Sep;30(5):649-58. doi: 10.1007/s10875-010-9429-y. Epub 2010 Jun 9.
• [5] Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer.Nat Commun. 2019 Jun 28;10(1):2860. doi: 10.1038/s41467-019-10743-7.
• [6] Use of the tumor repressor DEDD as a prognostic marker of cancer metastasis.Methods Mol Biol. 2014;1165:197-222. doi: 10.1007/978-1-4939-0856-1_14.
• [7] MCL1 and DEDD Promote Urothelial Carcinoma Progression.Mol Cancer Res. 2019 Jun;17(6):1294-1304. doi: 10.1158/1541-7786.MCR-18-0963. Epub 2019 Feb 18.
• [8] MicroRNA-17 inhibition overcomes chemoresistance and suppresses epithelial-mesenchymal transition through a DEDD-dependent mechanism in gastric cancer.Int J Biochem Cell Biol. 2018 Sep;102:59-70. doi: 10.1016/j.biocel.2018.06.007. Epub 2018 Jun 25.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [14] Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
• [15] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [16] 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.
• [17] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.