Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAPG2L5)

• DOT Name: Transcription elongation factor A protein-like 1 (TCEAL1)
• Synonyms: TCEA-like protein 1; Nuclear phosphoprotein p21/SIIR; Transcription elongation factor S-II protein-like 1
• Gene Name: TCEAL1
• Related Disease:
  Esophageal cancer
  Squamous cell neoplasm
  Bone osteosarcoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Hepatitis
  Hepatitis A virus infection
  Hepatitis B virus infection
  Lung cancer
  Lung carcinoma
  Neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked
  Osteosarcoma
  Renal cell carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Ulcerative colitis
  Advanced cancer
• UniProt ID: TCAL1_HUMAN
• Pfam ID: PF04538
• Sequence:
  MDKPRKENEEEPQSAPKTDEERPPVEHSPEKQSPEEQSSEEQSSEEEFFPEELLPELLPE
  MLLSEERPPQEGLSRKDLFEGRPPMEQPPCGVGKHKLEEGSFKERLARSRPQFRGDIHGR
  NLSNEEMIQAADELEEMKRVRNKLMIMHWKAKRSRPYPI
• Function: May be involved in transcriptional regulation. Modulates various viral and cellular promoters in a promoter context-dependent manner. For example, transcription from the FOS promoter is increased, while Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter activity is repressed. Does not bind DNA directly.
• Tissue Specificity: Expressed in all tissues examined. Highly expressed in heart, ovary, prostate and skeletal muscle. Moderately expressed in brain, placenta, testis and small intestine. Weakly expressed in lung, liver and spleen. Expressed in several cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal cancer	DISGB2VN	Definitive	Altered Expression	[1]
Squamous cell neoplasm	DISKBRLI	Definitive	Altered Expression	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[5]
Hepatitis	DISXXX35	Strong	Altered Expression	[6]
Hepatitis A virus infection	DISUMFQV	Strong	Altered Expression	[6]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[7]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[7]
Neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked	DISZ8K7C	Strong	X-linked	[8]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[10]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[11]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[12]

12 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 Transcription elongation factor A protein-like 1 (TCEAL1).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[19]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[20]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[21]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[24]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Transcription elongation factor A protein-like 1 (TCEAL1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription elongation factor A protein-like 1 (TCEAL1).	[23]

References

• [1] Differential expression of TCEAL1 in esophageal cancers by custom cDNA microarray analysis.Dis Esophagus. 2005;18(1):37-40. doi: 10.1111/j.1442-2050.2005.00432.x.
• [2] p21WAF1/CIP1 gene DNA sequencing and its expression in human osteosarcoma.Chin Med J (Engl). 2004 Jun;117(6):936-40.
• [3] Double stranded-RNA-mediated activation of P21 gene induced apoptosis and cell cycle arrest in renal cell carcinoma.Int J Cancer. 2009 Jul 15;125(2):446-52. doi: 10.1002/ijc.24370.
• [4] Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth.Oncotarget. 2017 Apr 11;8(15):25055-25065. doi: 10.18632/oncotarget.15918.
• [5] Polymorphisms in the 5' upstream regulatory region of p21(WAF1/CIP1) and susceptibility to oesophageal squamous cell carcinoma.Sci Rep. 2016 Mar 2;6:22564. doi: 10.1038/srep22564.
• [6] P21 expression and its relation to disease activity and hepatocyte proliferation in chronic hepatitis B virus infection.Turk J Gastroenterol. 2005 Mar;16(1):12-6.
• [7] Comprehensive assessment of P21 polymorphisms and lung cancer risk.J Hum Genet. 2008;53(1):87-95. doi: 10.1007/s10038-007-0222-6. Epub 2007 Nov 28.
• [8] A microdeletion at Xq22.2 implicates a glycine receptor GLRA4 involved in intellectual disability, behavioral problems and craniofacial anomalies. BMC Neurol. 2016 Aug 9;16:132. doi: 10.1186/s12883-016-0642-z.
• [9] Genetic variation in the 3'-untranslated region of PAK1 influences schizophrenia susceptibility.Exp Ther Med. 2017 Mar;13(3):1101-1108. doi: 10.3892/etm.2017.4039. Epub 2017 Jan 12.
• [10] P21/ WAF1 and cyclin D1 variants and oral squamous cell carcinoma.J Oral Pathol Med. 2008 Mar;37(3):151-6. doi: 10.1111/j.1600-0714.2007.00604.x.
• [11] Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis.J Gastroenterol Hepatol. 2018 Dec;33(12):1975-1983. doi: 10.1111/jgh.14297. Epub 2018 Jul 18.
• [12] Self-assembling HA/PEI/dsRNA-p21 ternary complexes for CD44 mediated small active RNA delivery to colorectal cancer.Drug Deliv. 2017 Nov;24(1):1537-1548. doi: 10.1080/10717544.2017.1386732.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [16] 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.
• [17] 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.
• [18] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [19] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [20] Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells. Br J Cancer. 2007 Oct 22;97(8):1099-105. doi: 10.1038/sj.bjc.6604003. Epub 2007 Sep 25.
• [21] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [22] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [23] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.