General Information of Drug Off-Target (DOT) (ID: OTIAC6W4)

DOT Name Core-binding factor subunit beta (CBFB)
Synonyms CBF-beta; Polyomavirus enhancer-binding protein 2 beta subunit; PEA2-beta; PEBP2-beta; SL3-3 enhancer factor 1 subunit beta; SL3/AKV core-binding factor beta subunit
Gene Name CBFB
Related Disease
Adenocarcinoma ( )
T-cell acute lymphoblastic leukaemia ( )
Acute myelomonocytic leukemia M4 ( )
Advanced cancer ( )
Bone development disease ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Chromosomal disorder ( )
Cleidocranial dysplasia 2 ( )
Epithelial ovarian cancer ( )
Estrogen-receptor positive breast cancer ( )
Gastric cancer ( )
Gastric neoplasm ( )
Hematologic disease ( )
Hepatitis B virus infection ( )
Immunodeficiency ( )
Isolated cleft palate ( )
Leukopenia ( )
Myelodysplastic syndrome ( )
Myeloid leukaemia ( )
Neoplasm ( )
Osteoporosis ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Stomach cancer ( )
Wilms tumor ( )
Systemic mastocytosis ( )
Acute lymphocytic leukaemia ( )
Acute leukaemia ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Childhood acute lymphoblastic leukemia ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
leukaemia ( )
Leukemia ( )
Small lymphocytic lymphoma ( )
UniProt ID
PEBB_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1CL3; 1E50; 1H9D; 4N9F; 6NIL; 6P59; 6VGD; 6VGE; 6VGG; 8CX0; 8CX1; 8CX2; 8E40; 8FVI; 8FVJ; 8H0I; 8J62
Pfam ID
PF02312
Sequence
MPRVVPDQRSKFENEEFFRKLSRECEIKYTGFRDRPHEERQARFQNACRDGRSEIAFVAT
GTNLSLQFFPASWQGEQRQTPSREYVDLEREAGKVYLKAPMILNGVCVIWKGWIDLQRLD
GMGCLEFDEERAQQEDALAQQAFEEARRRTREFEDRDRSHREEMEVRVSQLLAVTGKKTT
RP
Function
Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation.
Reactome Pathway
Transcriptional regulation by RUNX2 (R-HSA-8878166 )
RUNX1 regulates estrogen receptor mediated transcription (R-HSA-8931987 )
Regulation of RUNX1 Expression and Activity (R-HSA-8934593 )
RUNX1 regulates expression of components of tight junctions (R-HSA-8935964 )
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459 )
RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236 )
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes (R-HSA-8939242 )
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243 )
RUNX1 regulates transcription of genes involved in BCR signaling (R-HSA-8939245 )
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells (R-HSA-8939246 )
RUNX1 regulates transcription of genes involved in interleukin signaling (R-HSA-8939247 )
RUNX1 regulates transcription of genes involved in WNT signaling (R-HSA-8939256 )
Regulation of RUNX2 expression and activity (R-HSA-8939902 )
RUNX2 regulates osteoblast differentiation (R-HSA-8940973 )
RUNX2 regulates chondrocyte maturation (R-HSA-8941284 )
RUNX2 regulates bone development (R-HSA-8941326 )
RUNX2 regulates genes involved in cell migration (R-HSA-8941332 )
RUNX2 regulates genes involved in differentiation of myeloid cells (R-HSA-8941333 )
Regulation of RUNX3 expression and activity (R-HSA-8941858 )
RUNX3 Regulates Immune Response and Cell Migration (R-HSA-8949275 )
RUNX3 regulates RUNX1-mediated transcription (R-HSA-8951911 )
RUNX3 regulates p14-ARF (R-HSA-8951936 )
Estrogen-dependent gene expression (R-HSA-9018519 )
Transcriptional regulation of granulopoiesis (R-HSA-9616222 )
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) (R-HSA-8877330 )

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Definitive Genetic Variation [1]
T-cell acute lymphoblastic leukaemia DIS17AI2 Definitive Biomarker [2]
Acute myelomonocytic leukemia M4 DISRRMV2 Strong Genetic Variation [3]
Advanced cancer DISAT1Z9 Strong Genetic Variation [4]
Bone development disease DISVKAZS Strong Biomarker [5]
Bone osteosarcoma DIST1004 Strong Altered Expression [6]
Breast cancer DIS7DPX1 Strong Biomarker [4]
Breast carcinoma DIS2UE88 Strong Biomarker [4]
Chromosomal disorder DISM5BB5 Strong Biomarker [7]
Cleidocranial dysplasia 2 DISLTJ8W Strong Autosomal dominant [8]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [9]
Estrogen-receptor positive breast cancer DIS1H502 Strong Genetic Variation [10]
Gastric cancer DISXGOUK Strong Biomarker [11]
Gastric neoplasm DISOKN4Y Strong Altered Expression [11]
Hematologic disease DIS9XD9A Strong Biomarker [12]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [13]
Immunodeficiency DIS093I0 Strong Biomarker [14]
Isolated cleft palate DISV80CD Strong Biomarker [5]
Leukopenia DISJMBMM Strong Genetic Variation [15]
Myelodysplastic syndrome DISYHNUI Strong Altered Expression [16]
Myeloid leukaemia DISMN944 Strong Biomarker [17]
Neoplasm DISZKGEW Strong Genetic Variation [18]
Osteoporosis DISF2JE0 Strong Biomarker [19]
Osteosarcoma DISLQ7E2 Strong Altered Expression [6]
Ovarian cancer DISZJHAP Strong Biomarker [9]
Ovarian neoplasm DISEAFTY Strong Biomarker [9]
Stomach cancer DISKIJSX Strong Biomarker [11]
Wilms tumor DISB6T16 Strong Altered Expression [20]
Systemic mastocytosis DISNQ2OY moderate Genetic Variation [21]
Acute lymphocytic leukaemia DISPX75S Disputed Genetic Variation [22]
Acute leukaemia DISDQFDI Limited Genetic Variation [23]
Acute monocytic leukemia DIS28NEL Limited Genetic Variation [24]
Acute myelogenous leukaemia DISCSPTN Limited Unknown [25]
Childhood acute lymphoblastic leukemia DISJ5D6U Limited Genetic Variation [26]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [27]
Colorectal neoplasm DISR1UCN Limited Altered Expression [27]
leukaemia DISS7D1V Limited Altered Expression [28]
Leukemia DISNAKFL Limited Altered Expression [28]
Small lymphocytic lymphoma DIS30POX Limited Biomarker [29]
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⏷ Show the Full List of 39 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
21 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Core-binding factor subunit beta (CBFB). [30]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Core-binding factor subunit beta (CBFB). [31]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Core-binding factor subunit beta (CBFB). [32]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Core-binding factor subunit beta (CBFB). [33]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Core-binding factor subunit beta (CBFB). [34]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Core-binding factor subunit beta (CBFB). [35]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Core-binding factor subunit beta (CBFB). [36]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Core-binding factor subunit beta (CBFB). [37]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Core-binding factor subunit beta (CBFB). [39]
Marinol DM70IK5 Approved Marinol decreases the expression of Core-binding factor subunit beta (CBFB). [40]
Menadione DMSJDTY Approved Menadione affects the expression of Core-binding factor subunit beta (CBFB). [39]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Core-binding factor subunit beta (CBFB). [41]
Malathion DMXZ84M Approved Malathion increases the expression of Core-binding factor subunit beta (CBFB). [42]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial increases the expression of Core-binding factor subunit beta (CBFB). [43]
Motexafin gadolinium DMEJKRF Approved Motexafin gadolinium increases the expression of Core-binding factor subunit beta (CBFB). [43]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Core-binding factor subunit beta (CBFB). [44]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Core-binding factor subunit beta (CBFB). [45]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Core-binding factor subunit beta (CBFB). [46]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Core-binding factor subunit beta (CBFB). [48]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Core-binding factor subunit beta (CBFB). [36]
geraniol DMS3CBD Investigative geraniol decreases the expression of Core-binding factor subunit beta (CBFB). [49]
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⏷ Show the Full List of 21 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Core-binding factor subunit beta (CBFB). [38]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Core-binding factor subunit beta (CBFB). [47]
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References

1 Landscape of genomic alterations in cervical carcinomas.Nature. 2014 Feb 20;506(7488):371-5. doi: 10.1038/nature12881. Epub 2013 Dec 25.
2 RUNX1 is required for oncogenic Myb and Myc enhancer activity in T-cell acute lymphoblastic leukemia.Blood. 2017 Oct 12;130(15):1722-1733. doi: 10.1182/blood-2017-03-775536. Epub 2017 Aug 8.
3 Detection of a novel CBFB/MYH11 variant fusion transcript (K-type) showing partial insertion of exon 6 of CBFB gene using two commercially available multiplex RT-PCR kits.Cancer Genet Cytogenet. 2009 Mar;189(2):87-92. doi: 10.1016/j.cancergencyto.2008.10.012.
4 The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription.Nat Commun. 2019 May 6;10(1):2071. doi: 10.1038/s41467-019-10102-6.
5 Core binding factor beta (CBFB) haploinsufficiency due to an interstitial deletion at 16q21q22 resulting in delayed cranial ossification, cleft palate, congenital heart anomalies, and feeding difficulties but favorable outcome.Am J Med Genet A. 2006 Nov 1;140(21):2349-54. doi: 10.1002/ajmg.a.31479.
6 Transcriptional activation of CBF by CDK11(p110) is necessary to promote osteosarcoma cell proliferation.Cell Commun Signal. 2019 Oct 14;17(1):125. doi: 10.1186/s12964-019-0440-5.
7 Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22).Cancer Genet. 2020 Feb;241:72-76. doi: 10.1016/j.cancergen.2019.07.005. Epub 2019 Jul 24.
8 Heterozygous pathogenic variants involving CBFB cause a new skeletal disorder resembling cleidocranial dysplasia. J Med Genet. 2023 May;60(5):498-504. doi: 10.1136/jmg-2022-108739. Epub 2022 Oct 14.
9 Small molecule inhibition of the CBF/RUNX interaction decreases ovarian cancer growth and migration through alterations in genes related to epithelial-to-mesenchymal transition.Gynecol Oncol. 2018 May;149(2):350-360. doi: 10.1016/j.ygyno.2018.03.005. Epub 2018 Mar 16.
10 Genome-wide association study of germline variants and breast cancer-specific mortality.Br J Cancer. 2019 Mar;120(6):647-657. doi: 10.1038/s41416-019-0393-x. Epub 2019 Feb 21.
11 Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer.Int J Cancer. 2005 Jan 10;113(2):221-8. doi: 10.1002/ijc.20551.
12 Clinical Relevance of RUNX1 and CBFB Alterations in Acute Myeloid Leukemia and Other Hematological Disorders.Adv Exp Med Biol. 2017;962:175-199. doi: 10.1007/978-981-10-3233-2_12.
13 Type III interferon-induced CBF inhibits HBV replication by hijacking HBx.Cell Mol Immunol. 2019 Apr;16(4):357-366. doi: 10.1038/s41423-018-0006-2. Epub 2018 Mar 9.
14 Vif proteins of human and simian immunodeficiency viruses require cellular CBF to degrade APOBEC3 restriction factors.J Virol. 2012 Mar;86(5):2874-7. doi: 10.1128/JVI.06950-11. Epub 2011 Dec 28.
15 Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients.Leukemia. 2007 Apr;21(4):725-31. doi: 10.1038/sj.leu.2404531. Epub 2007 Feb 8.
16 Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia.Front Oncol. 2018 Apr 26;8:129. doi: 10.3389/fonc.2018.00129. eCollection 2018.
17 Coexistence of p210(BCR-ABL) and CBF-MYH11 fusion genes in myeloid leukemia: A report of 4 cases.Oncol Lett. 2017 Nov;14(5):5171-5178. doi: 10.3892/ol.2017.6812. Epub 2017 Aug 24.
18 Myeloid neoplasms with concurrent BCR-ABL1 and CBFB rearrangements: A series of 10 cases of a clinically aggressive neoplasm.Am J Hematol. 2017 Jun;92(6):520-528. doi: 10.1002/ajh.24710. Epub 2017 Apr 6.
19 Cbf governs osteoblast-adipocyte lineage commitment through enhancing -catenin signaling and suppressing adipogenesis gene expression.Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10119-10124. doi: 10.1073/pnas.1619294114. Epub 2017 Sep 1.
20 Quantitative assessment of Wilms tumor 1 expression by real-time quantitative polymerase chain reaction in patients with acute myeloblastic leukemia.J Res Med Sci. 2017 Apr 26;22:54. doi: 10.4103/jrms.JRMS_448_16. eCollection 2017.
21 Systemic mastocytosis is uncommon in KIT D816V mutation positive core-binding factor acute myeloid leukemia.Leuk Lymphoma. 2012 Jul;53(7):1338-44. doi: 10.3109/10428194.2011.647314. Epub 2012 Jan 31.
22 The incidence of submicroscopic deletions in reciprocal translocations is similar in acute myeloid leukemia, BCR-ABL positive acute lymphoblastic leukemia, and chronic myeloid leukemia.Haematologica. 2005 Apr;90(4):558-9.
23 Downregulation of RUNX1/CBF by MLL fusion proteins enhances hematopoietic stem cell self-renewal.Blood. 2014 Mar 13;123(11):1729-38. doi: 10.1182/blood-2013-03-489575. Epub 2014 Jan 21.
24 Randomized phase-II trial evaluating induction therapy with idarubicin and etoposide plus sequential or concurrent azacitidine and maintenance therapy with azacitidine.Leukemia. 2019 Aug;33(8):1923-1933. doi: 10.1038/s41375-019-0395-y. Epub 2019 Feb 6.
25 Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet. 2002 Dec;32(4):633-8. doi: 10.1038/ng1015. Epub 2002 Nov 18.
26 Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBF interaction.Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14592-7. doi: 10.1073/pnas.1200037109. Epub 2012 Aug 21.
27 Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer.Br J Cancer. 2009 Feb 10;100(3):511-23. doi: 10.1038/sj.bjc.6604884. Epub 2009 Jan 20.
28 CBF-SMMHC Inhibition Triggers Apoptosis by Disrupting MYC Chromatin Dynamics in Acute Myeloid Leukemia.Cell. 2018 Jun 28;174(1):172-186.e21. doi: 10.1016/j.cell.2018.05.048.
29 Circular RNA circ-CBFB promotes proliferation and inhibits apoptosis in chronic lymphocytic leukemia through regulating miR-607/FZD3/Wnt/-catenin pathway.Biochem Biophys Res Commun. 2018 Sep 3;503(1):385-390. doi: 10.1016/j.bbrc.2018.06.045. Epub 2018 Jun 15.
30 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
31 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.
32 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.
33 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
34 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.
35 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
36 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
37 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
38 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
39 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.
40 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
41 Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
42 Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
43 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
44 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
45 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
46 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
47 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
48 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
49 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.