Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDLL4NB)

DOT Name Poly(rC)-binding protein 4 (PCBP4)
Synonyms Alpha-CP4
Gene Name PCBP4
Related Disease
Bone osteosarcoma ( )
Intellectual disability ( )
leukaemia ( )
Osteosarcoma ( )
Rheumatoid arthritis ( )
Rubinstein-Taybi syndrome ( )
Acute leukaemia ( )
Acute lymphocytic leukaemia ( )
Acute myelomonocytic leukemia M4 ( )
Advanced cancer ( )
Alzheimer disease ( )
Autoimmune disease ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Endometrial carcinoma ( )
Esophageal squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Huntington disease ( )
Leukemia ( )
Lung neoplasm ( )
Non-small-cell lung cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Squamous cell carcinoma ( )
Status epilepticus seizure ( )
Thyroid gland papillary carcinoma ( )
Triple negative breast cancer ( )
Type-1/2 diabetes ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
High blood pressure ( )
Lung adenocarcinoma ( )
Plasma cell myeloma ( )
Childhood acute lymphoblastic leukemia ( )
Acute myelogenous leukaemia ( )
Gastric cancer ( )
Lymphoma ( )
Melanoma ( )
Nasopharyngeal carcinoma ( )
Rett syndrome ( )
Rothmund-Thomson syndrome ( )
Stomach cancer ( )
Type-1 diabetes ( )
UniProt ID
PCBP4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00013
Sequence
MSGSDGGLEEEPELSITLTLRMLMHGKEVGSIIGKKGETVKRIREQSSARITISEGSCPE
RITTITGSTAAVFHAVSMIAFKLDEDLCAAPANGGNVSRPPVTLRLVIPASQCGSLIGKA
GTKIKEIRETTGAQVQVAGDLLPNSTERAVTVSGVPDAIILCVRQICAVILESPPKGATI
PYHPSLSLGTVLLSANQGFSVQGQYGAVTPAEVTKLQQLSSHAVPFATPSVVPGLDPGTQ
TSSQEFLVPNDLIGCVIGRQGSKISEIRQMSGAHIKIGNQAEGAGERHVTITGSPVSIAL
AQYLITACLETAKSTSGGTPSSAPADLPAPFSPPLTALPTAPPGLLGTPYAISLSNFIGL
KPMPFLALPPASPGPPPGLAAYTAKMAAANGSKKAERQKFSPY
Function Single-stranded nucleic acid binding protein that binds preferentially to oligo dC.
Reactome Pathway
Transcriptional activation of cell cycle inhibitor p21 (R-HSA-69895 )
FOXO-mediated transcription of cell cycle genes (R-HSA-9617828 )
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bone osteosarcoma DIST1004 Definitive Biomarker [1]
Intellectual disability DISMBNXP Definitive Genetic Variation [2]
leukaemia DISS7D1V Definitive Genetic Variation [3]
Osteosarcoma DISLQ7E2 Definitive Biomarker [1]
Rheumatoid arthritis DISTSB4J Definitive Biomarker [4]
Rubinstein-Taybi syndrome DISVF1HM Definitive Biomarker [5]
Acute leukaemia DISDQFDI Strong Genetic Variation [6]
Acute lymphocytic leukaemia DISPX75S Strong Biomarker [7]
Acute myelomonocytic leukemia M4 DISRRMV2 Strong Genetic Variation [8]
Advanced cancer DISAT1Z9 Strong Biomarker [9]
Alzheimer disease DISF8S70 Strong Biomarker [10]
Autoimmune disease DISORMTM Strong Genetic Variation [11]
Bladder cancer DISUHNM0 Strong Biomarker [12]
Breast cancer DIS7DPX1 Strong Biomarker [13]
Breast carcinoma DIS2UE88 Strong Biomarker [13]
Colon cancer DISVC52G Strong Biomarker [14]
Colon carcinoma DISJYKUO Strong Biomarker [14]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [15]
Endometrial carcinoma DISXR5CY Strong Altered Expression [16]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [17]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [18]
Huntington disease DISQPLA4 Strong Altered Expression [19]
Leukemia DISNAKFL Strong Genetic Variation [3]
Lung neoplasm DISVARNB Strong Altered Expression [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [21]
Prostate cancer DISF190Y Strong Biomarker [22]
Prostate carcinoma DISMJPLE Strong Biomarker [22]
Squamous cell carcinoma DISQVIFL Strong Biomarker [23]
Status epilepticus seizure DISY3BIC Strong Altered Expression [24]
Thyroid gland papillary carcinoma DIS48YMM Strong Biomarker [25]
Triple negative breast cancer DISAMG6N Strong Biomarker [26]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [27]
Ulcerative colitis DIS8K27O Strong Biomarker [28]
Urinary bladder cancer DISDV4T7 Strong Biomarker [12]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [12]
High blood pressure DISY2OHH moderate Biomarker [29]
Lung adenocarcinoma DISD51WR moderate Biomarker [30]
Plasma cell myeloma DIS0DFZ0 moderate Altered Expression [31]
Childhood acute lymphoblastic leukemia DISJ5D6U Disputed Altered Expression [3]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [32]
Gastric cancer DISXGOUK Limited Altered Expression [33]
Lymphoma DISN6V4S Limited Biomarker [34]
Melanoma DIS1RRCY Limited Biomarker [35]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [36]
Rett syndrome DISGG5UV Limited Biomarker [37]
Rothmund-Thomson syndrome DISGVBCV Limited Biomarker [37]
Stomach cancer DISKIJSX Limited Altered Expression [33]
Type-1 diabetes DIS7HLUB Limited Biomarker [38]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Poly(rC)-binding protein 4 (PCBP4). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Poly(rC)-binding protein 4 (PCBP4). [45]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Poly(rC)-binding protein 4 (PCBP4). [40]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Poly(rC)-binding protein 4 (PCBP4). [41]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Poly(rC)-binding protein 4 (PCBP4). [42]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of Poly(rC)-binding protein 4 (PCBP4). [43]
Delphinidin DMS2WIN Phase 2 Delphinidin affects the expression of Poly(rC)-binding protein 4 (PCBP4). [44]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Poly(rC)-binding protein 4 (PCBP4). [46]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Poly(rC)-binding protein 4 (PCBP4). [47]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Poly(rC)-binding protein 4 (PCBP4). [48]
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⏷ Show the Full List of 8 Drug(s)

References

1 Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP.Cancer Manag Res. 2019 Oct 24;11:9153-9163. doi: 10.2147/CMAR.S219535. eCollection 2019.
2 The transcriptional coactivator and histone acetyltransferase CBP regulates neural precursor cell development and migration.Acta Neuropathol Commun. 2019 Dec 5;7(1):199. doi: 10.1186/s40478-019-0849-5.
3 Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia.Oncogene. 2014 Apr 24;33(17):2169-78. doi: 10.1038/onc.2013.169. Epub 2013 Jun 3.
4 TNF- induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells.Biochem Biophys Res Commun. 2018 Jan 8;495(2):1675-1680. doi: 10.1016/j.bbrc.2017.12.015. Epub 2017 Dec 5.
5 Mutations in CREBBP and EP300 genes affect DNA repair of oxidative damage in Rubinstein-Taybi syndrome cells.Carcinogenesis. 2020 May 14;41(3):257-266. doi: 10.1093/carcin/bgz149.
6 SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3.Cancer Res. 2000 Feb 15;60(4):1139-45.
7 CBP Modulates Sensitivity to Dasatinib in Pre-BCR(+) Acute Lymphoblastic Leukemia.Cancer Res. 2018 Nov 15;78(22):6497-6508. doi: 10.1158/0008-5472.CAN-18-1703. Epub 2018 Sep 27.
8 RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.Leukemia. 2004 Jun;18(6):1115-21. doi: 10.1038/sj.leu.2403353.
9 Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP.Biochemistry. 2019 Apr 23;58(16):2133-2143. doi: 10.1021/acs.biochem.9b00160. Epub 2019 Apr 11.
10 A-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer's disease.Mol Neurodegener. 2015 Mar 19;10:13. doi: 10.1186/s13024-015-0007-x.
11 Two histone/protein acetyltransferases, CBP and p300, are indispensable for Foxp3+ T-regulatory cell development and function.Mol Cell Biol. 2014 Nov;34(21):3993-4007. doi: 10.1128/MCB.00919-14. Epub 2014 Aug 25.
12 A CRISPR Interference of CBP and p300 Selectively Induced Synthetic Lethality in Bladder Cancer Cells In Vitro.Int J Biol Sci. 2019 May 11;15(6):1276-1286. doi: 10.7150/ijbs.32332. eCollection 2019.
13 Small molecule nAS-E targeting cAMP response element binding protein (CREB) and CREB-binding protein interaction inhibits breast cancer bone metastasis.J Cell Mol Med. 2019 Feb;23(2):1224-1234. doi: 10.1111/jcmm.14024. Epub 2018 Nov 20.
14 Interactions between XIAP associated factor 1 and a nuclear co-activator, CBP, in colon cancer cells.Digestion. 2008;77(2):79-86. doi: 10.1159/000121441. Epub 2008 Mar 21.
15 Aberrant activation of CYR61 enhancers in colorectal cancer development.J Exp Clin Cancer Res. 2019 May 22;38(1):213. doi: 10.1186/s13046-019-1217-9.
16 Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression.Cancer. 2003 Nov 15;98(10):2207-13. doi: 10.1002/cncr.11760.
17 A novel long noncoding RNA linc00460 up-regulated by CBP/P300 promotes carcinogenesis in esophageal squamous cell carcinoma.Biosci Rep. 2017 Oct 17;37(5):BSR20171019. doi: 10.1042/BSR20171019. Print 2017 Oct 31.
18 Inhibition of the Wnt/-catenin signaling pathway improves the anti-tumor effects of sorafenib against hepatocellular carcinoma.Cancer Lett. 2016 Oct 10;381(1):58-66. doi: 10.1016/j.canlet.2016.07.013. Epub 2016 Jul 16.
19 Neuroprotective effects of psychotropic drugs in Huntington's disease.Int J Mol Sci. 2013 Nov 15;14(11):22558-603. doi: 10.3390/ijms141122558.
20 Expression of alpha CP-4 inhibits cell cycle progression and suppresses tumorigenicity of lung cancer cells.Int J Cancer. 2008 Apr 1;122(7):1512-20. doi: 10.1002/ijc.23236.
21 Alpha CP-4, encoded by a putative tumor suppressor gene at 3p21, but not its alternative splice variant alpha CP-4a, is underexpressed in lung cancer.Cancer Res. 2004 Jun 15;64(12):4171-9. doi: 10.1158/0008-5472.CAN-03-2982.
22 The novel BET-CBP/p300 dual inhibitor NEO2734 is active in SPOP mutant and wild-type prostate cancer.EMBO Mol Med. 2019 Nov 7;11(11):e10659. doi: 10.15252/emmm.201910659. Epub 2019 Sep 26.
23 Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines.Jpn J Cancer Res. 2001 Jan;92(1):42-50. doi: 10.1111/j.1349-7006.2001.tb01046.x.
24 The Epigenetic Factor CBP Is Required for the Differentiation and Function of Medial Ganglionic Eminence-Derived Interneurons.Mol Neurobiol. 2019 Jun;56(6):4440-4454. doi: 10.1007/s12035-018-1382-4. Epub 2018 Oct 17.
25 CITED1 promotes proliferation of papillary thyroid cancer cells via the regulation of p21 and p27.Cell Biosci. 2018 Nov 6;8:57. doi: 10.1186/s13578-018-0256-9. eCollection 2018.
26 Novel Copper Complexes That Inhibit the Proteasome and Trigger Apoptosis in Triple-Negative Breast Cancer Cells.ACS Med Chem Lett. 2019 Jul 25;10(9):1328-1335. doi: 10.1021/acsmedchemlett.9b00284. eCollection 2019 Sep 12.
27 Insulin Downregulates the Transcriptional Coregulator CITED2, an Inhibitor of Proangiogenic Function in Endothelial Cells.Diabetes. 2016 Dec;65(12):3680-3690. doi: 10.2337/db16-0001. Epub 2016 Aug 25.
28 Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.Oxid Med Cell Longev. 2017;2017:9303158. doi: 10.1155/2017/9303158. Epub 2017 Jun 7.
29 Morbidity After Cardiac Surgery in Patients With Adult Congenital Heart Disease in Comparison With Acquired Disease.Heart Lung Circ. 2018 Jun;27(6):739-744. doi: 10.1016/j.hlc.2017.05.133. Epub 2017 Jun 28.
30 GATA3 acetylation at K119 by CBP inhibits cell migration and invasion in lung adenocarcinoma.Biochem Biophys Res Commun. 2018 Mar 4;497(2):633-638. doi: 10.1016/j.bbrc.2018.02.120. Epub 2018 Feb 14.
31 Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4.Blood Cancer J. 2019 Feb 11;9(2):19. doi: 10.1038/s41408-019-0173-0.
32 Transcriptional regulators CITED2 and PU.1 cooperate in maintaining hematopoietic stem cells.Exp Hematol. 2019 May;73:38-49.e7. doi: 10.1016/j.exphem.2019.03.003. Epub 2019 Apr 13.
33 Down-regulation of a pro-apoptotic pathway regulated by PCAF/ADA3 in early stage gastric cancer.Cell Death Dis. 2018 May 1;9(5):442. doi: 10.1038/s41419-018-0470-8.
34 Epigenetics and B-cell lymphoma.Curr Opin Hematol. 2011 Jul;18(4):293-9. doi: 10.1097/MOH.0b013e32834788cf.
35 A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity.Cell Death Dis. 2015 Feb 12;6(2):e1634. doi: 10.1038/cddis.2015.17.
36 Therapeutic targeting of CBP/-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin.Sci Rep. 2015 Apr 21;5:9979. doi: 10.1038/srep09979.
37 Mutation of the CH1 Domain in the Histone Acetyltransferase CREBBP Results in Autism-Relevant Behaviors in Mice.PLoS One. 2016 Jan 5;11(1):e0146366. doi: 10.1371/journal.pone.0146366. eCollection 2016.
38 Persistent STAT5 phosphorylation and epigenetic dysregulation of GM-CSF and PGS2/COX2 expression in Type 1 diabetic human monocytes.PLoS One. 2013 Oct 18;8(10):e76919. doi: 10.1371/journal.pone.0076919. eCollection 2013.
39 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.
40 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.
41 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.
42 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
43 Role of DNA Repair Pathways in Response to Zidovudine-induced DNA Damage in Immortalized Human Liver THLE2 Cells. Int J Biomed Sci. 2013 Mar;9(1):18-25.
44 Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons. Chem Res Toxicol. 2009 Mar 16;22(3):554-64. doi: 10.1021/tx800293v.
45 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.
46 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.
47 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.
48 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.