[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/bcl3-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki24\/bcl3-wikipedia\/","headline":"BCL3 – Wikipedia","name":"BCL3 – Wikipedia","description":"From Wikipedia, the free encyclopedia Protein-coding gene in the species Homo sapiens B-cell lymphoma 3-encoded protein is a protein that","datePublished":"2015-10-08","dateModified":"2015-10-08","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/f\/fa\/PDB_1k1a_EBI.jpg\/180px-PDB_1k1a_EBI.jpg","url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/f\/fa\/PDB_1k1a_EBI.jpg\/180px-PDB_1k1a_EBI.jpg","height":"135","width":"180"},"url":"https:\/\/wiki.edu.vn\/en\/wiki24\/bcl3-wikipedia\/","wordCount":12618,"articleBody":"From Wikipedia, the free encyclopediaProtein-coding gene in the species Homo sapiensB-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.[5][6]This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional coactivator that activates through its association with NF-kappa B homodimers. The expression of this gene can be induced by NF-kappa B, which forms a part of the autoregulatory loop that controls the nuclear residence of p50 NF-kappa B.[7]Like BCL2, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.Table of ContentsInteractions[edit]Clinical significance[edit]Role in cancer therapy[edit]References[edit]Further reading[edit]External links[edit]Interactions[edit]BCL3 has been shown to interact with:BARD1,[8]C-Fos,[9]C-jun,[9]C22orf25,[10]COPS5,[8]EP300,[9]HTATIP,[8]NFKB1,[11][12][13]NFKB2,[11][14]PIR,[8]  andNR2B1.[15]Clinical significance[edit]Genetic variations in BCL3 gene have been associated with late-onset Alzheimer’s disease (LOAD) and chronic lymphocytic leukemia. \u03b2-amyloid accumulation in neurons of Alzheimer’s patients results in activation of NF-\u03baB, which induces BCL3 expression.[16] Increased expression of BCL3 has been observed in the brains of patients with LOAD.[17]The role of Bcl3 in solid tumors was established through the ability of Bcl3 to promote metastasis without affecting primary tumor growth or normal mammary function, within models of ErbB2-positive breast cancer.[18] Further research has uncovered the role of Bcl3 in promoting progression of other solid tumors. The role of Bcl3 in promoting tumor hallmarks has been most widely reported for advanced colorectal cancer; where Bcl3 expression is up-regulated in >30% of colorectal cancer cases and is associated with a poor prognosis. For example, in colorectal cancer models, elevated Bcl3 expression was found to activate AKT signalling,[19] drive a cancer stem cell phenotype through enhancing \u03b2-catenin signalling,[20] drive the COX-2 mediated response to inflammatory cytokines,[21] and protect colorectal tumor cells against DNA damage.[22] The role of Bcl3 in enabling multiple cancer hallmarks in colorectal carcinogenesis has been reviewed.[23]More recently other cancer cell signalling pathways have been shown to be modulated by Bcl3.\u00a0These include Wnt\/beta-catenin through direct protein interaction;[20]Smad3, through an unknown mechanism of protein stabilisation[24] and transcriptional regulation of Stat3.[25][26]\u00a0Other pathways influenced by Bcl3 activity include phosphorylation of AKT through an unknown mechanism.[19]Role in cancer therapy[edit]Bcl3 also influences responses of cancer cells to treatment.\u00a0Bcl3 promotes resistance to alkylating chemotherapy in gliomas,[27] DNA damaging agents in colorectal cancer,[22] and regulates the cancer immune checkpoint control gene PD-L1 in ovarian cancer cells.[28]The first discovery of a small molecule anti-metastatic Bcl3 inhibitor was reported utilising a virtual drug design and screening approach, targeting the protein-protein interaction between Bcl3 and partner protein p50.[29] The virtual screening hit compound showed potent intracellular Bcl3-inhibitory activity, and led to reductions in NF-\u03baB signalling, tumor colony formation and cancer cell migration within in vitro cellular models of breast cancer. In vivo inhibition of tumor growth and anti-metastatic activity was observed in invasive breast cancer models, without overt systemic toxicity.References[edit]^ a b c GRCh38: Ensembl release 89: ENSG00000069399 – Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053175 – Ensembl, May 2017^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ Wulczyn FG, Naumann M, Scheidereit C (August 1992). “Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-kappa B”. Nature. 358 (6387): 597\u2013599. Bibcode:1992Natur.358..597W. doi:10.1038\/358597a0. PMID\u00a01501714. S2CID\u00a04363340.^ Ohno H, Takimoto G, McKeithan TW (March 1990). “The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control”. Cell. 60 (6): 991\u2013997. doi:10.1016\/0092-8674(90)90347-H. PMID\u00a02180580. S2CID\u00a01919787.^ “Entrez Gene: BCL3 B-cell CLL\/lymphoma 3”.^ a b c d Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG,  et\u00a0al. (June 1999). “The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB\/Rel and nuclear co-regulators”. Oncogene. 18 (22): 3316\u20133323. doi:10.1038\/sj.onc.1202717. PMID\u00a010362352.^ a b c Na SY, Choi JE, Kim HJ, Jhun BH, Lee YC, Lee JW (October 1999). “Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation”. The Journal of Biological Chemistry. 274 (40): 28491\u201328496. doi:10.1074\/jbc.274.40.28491. PMID\u00a010497212.^ “Molecular Interaction Database”. Archived from the original on 2006-05-06. Retrieved 2012-05-08.^ a b Thornburg NJ, Pathmanathan R, Raab-Traub N (December 2003). “Activation of nuclear factor-kappaB p50 homodimer\/Bcl-3 complexes in nasopharyngeal carcinoma”. Cancer Research. 63 (23): 8293\u20138301. PMID\u00a014678988.^ Naumann M, Wulczyn FG, Scheidereit C (January 1993). “The NF-kappa B precursor p105 and the proto-oncogene product Bcl-3 are I kappa B molecules and control nuclear translocation of NF-kappa B”. The EMBO Journal. 12 (1): 213\u2013222. doi:10.1002\/j.1460-2075.1993.tb05647.x. PMC\u00a0413194. PMID\u00a08428580.^ Heissmeyer V, Krappmann D, Wulczyn FG, Scheidereit C (September 1999). “NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of Bcl-3-p50 complexes”. The EMBO Journal. 18 (17): 4766\u20134778. doi:10.1093\/emboj\/18.17.4766. PMC\u00a01171549. PMID\u00a010469655.^ Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, Siebenlist U (March 1993). “The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers”. Cell. 72 (5): 729\u2013739. doi:10.1016\/0092-8674(93)90401-b. PMID\u00a08453667.^ Na SY, Choi HS, Kim JW, Na DS, Lee JW (November 1998). “Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor”. The Journal of Biological Chemistry. 273 (47): 30933\u201330938. doi:10.1074\/jbc.273.47.30933. PMID\u00a09812988.^ Nho K, Kim S, Horgusluoglu E, Risacher SL, Shen L, Kim D,  et\u00a0al. (May 2017). “Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer’s disease”. BMC Medical Genomics. 10 (Suppl 1): 29. doi:10.1186\/s12920-017-0267-0. PMC\u00a05461522. PMID\u00a028589856.^ Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D,  et\u00a0al. (September 2021). “A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease”. Nature Genetics. 53 (9): 1276\u20131282. doi:10.1038\/s41588-021-00921-z. hdl:1871.1\/61f01aa9-6dc7-4213-be2a-d3fe622db488. PMID\u00a034493870. S2CID\u00a0237442349.^ Wakefield A, Soukupova J, Montagne A, Ranger J, French R, Muller WJ, Clarkson RW (January 2013). “Bcl3 selectively promotes metastasis of ERBB2-driven mammary tumors”. Cancer Research. 73 (2): 745\u2013755. doi:10.1158\/0008-5472.CAN-12-1321. PMID\u00a023149915. S2CID\u00a0342425.^ a b Urban BC, Collard TJ, Eagle CJ, Southern SL, Greenhough A, Hamdollah-Zadeh M,  et\u00a0al. (July 2016). “BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling”. Gut. 65 (7): 1151\u20131164. doi:10.1136\/gutjnl-2014-308270. PMC\u00a04941180. PMID\u00a026033966.^ a b Legge DN, Shephard AP, Collard TJ, Greenhough A, Chambers AC, Clarkson RW,  et\u00a0al. (March 2019). “BCL-3 promotes a cancer stem cell phenotype by enhancing \u03b2-catenin signalling in colorectal tumour cells”. Disease Models & Mechanisms. 12 (3): dmm037697. doi:10.1242\/dmm.037697. PMC\u00a06451435. PMID\u00a030792270.^ Collard TJ, Fallatah HM, Greenhough A, Paraskeva C, Williams AC (May 2020). “BCL\u20113 promotes cyclooxygenase\u20112\/prostaglandin E2 signalling in colorectal cancer”. International Journal of Oncology. 56 (5): 1304\u20131313. doi:10.3892\/ijo.2020.5013. PMID\u00a032319612. S2CID\u00a0216073785.^ a b Parker C, Chambers AC, Flanagan DJ, Ho JW, Collard TJ, Ngo G,  et\u00a0al. (July 2022). “BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination”. DNA Repair. 115: 103331. doi:10.1016\/j.dnarep.2022.103331. PMID\u00a035468497. S2CID\u00a0248220856.^ Legge DN, Chambers AC, Parker CT, Timms P, Collard TJ, Williams AC (May 2020). “The role of B-Cell Lymphoma-3 (BCL-3) in enabling the hallmarks of cancer: implications for the treatment of colorectal carcinogenesis”. Carcinogenesis. 41 (3): 249\u2013256. doi:10.1093\/carcin\/bgaa003. PMC\u00a07221501. PMID\u00a031930327.^ Chen X, Cao X, Sun X, Lei R, Chen P, Zhao Y,  et\u00a0al. (December 2016). “Bcl-3 regulates TGF\u03b2 signaling by stabilizing Smad3 during breast cancer pulmonary metastasis”. Cell Death & Disease. 7 (12): e2508. doi:10.1038\/cddis.2016.405. PMC\u00a05261001. PMID\u00a027906182.^ Wu J, Li L, Jiang G, Zhan H, Wang N (December 2016). “B-cell CLL\/lymphoma 3 promotes glioma cell proliferation and inhibits apoptosis through the oncogenic STAT3 pathway”. International Journal of Oncology. 49 (6): 2471\u20132479. doi:10.3892\/ijo.2016.3729. PMID\u00a027748795.^ Zhao H, Wang W, Zhao Q, Hu G, Deng K, Liu Y (Oct 2016). “BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer”. OncoTargets and Therapy. 9: 6619\u20136629. doi:10.2147\/OTT.S118184. PMC\u00a05087794. PMID\u00a027822067.^ Wu L, Bernal GM, Cahill KE, Pytel P, Fitzpatrick CA, Mashek H,  et\u00a0al. (July 2018). “BCL3 expression promotes resistance to alkylating chemotherapy in gliomas”. Science Translational Medicine. 10 (448): eaar2238. doi:10.1126\/scitranslmed.aar2238. PMC\u00a06613219. PMID\u00a029973405.^ Zou Y, Uddin MM, Padmanabhan S, Zhu Y, Bu P, Vancura A, Vancurova I (October 2018). “The proto-oncogene Bcl3 induces immune checkpoint PD-L1 expression, mediating proliferation of ovarian cancer cells”. The Journal of Biological Chemistry. 293 (40): 15483\u201315496. doi:10.1074\/jbc.RA118.004084. PMC\u00a06177577. PMID\u00a030135206.^ Soukupov\u00e1 J, Bordoni C, Turnham DJ, Yang WW, Seaton G, Gruca A,  et\u00a0al. (May 2021). “The Discovery of a Novel Antimetastatic Bcl3 Inhibitor”. Molecular Cancer Therapeutics. 20 (5): 775\u2013786. doi:10.1158\/1535-7163.MCT-20-0283. PMID\u00a033649105. S2CID\u00a0232088625.Further reading[edit]Franzoso G, Bours V, Park S, Tomita-Yamaguchi M, Kelly K, Siebenlist U (September 1992). “The candidate oncoprotein Bcl-3 is an antagonist of p50\/NF-kappa B-mediated inhibition”. Nature. 359 (6393): 339\u2013342. Bibcode:1992Natur.359..339F. doi:10.1038\/359339a0. PMID\u00a01406939. S2CID\u00a04322739.Bhatia K, Huppi K, McKeithan T, Siwarski D, Mushinski JF, Magrath I (September 1991). “Mouse bcl-3: cDNA structure, mapping and stage-dependent expression in B lymphocytes”. Oncogene. 6 (9): 1569\u20131573. PMID\u00a01923524.Mills FC, Brooker JS, Camerini-Otero RD (December 1990). “Sequences of human immunoglobulin switch regions: implications for recombination and transcription”. Nucleic Acids Research. 18 (24): 7305\u20137316. doi:10.1093\/nar\/18.24.7305. PMC\u00a0332867. PMID\u00a02124350.Crossen PE, Kennedy MA, Heaton DC, Morrison MJ (September 1993). “Cloning and sequencing of a t(14;19) breakpoint that involves the C mu switch region”. Genes, Chromosomes & Cancer. 8 (1): 60\u201362. doi:10.1002\/gcc.2870080110. PMID\u00a07691160. S2CID\u00a085217954.McKeithan TW, Ohno H, Dickstein J, Hume E (November 1994). “Genomic structure of the candidate proto-oncogene BCL3”. Genomics. 24 (1): 120\u2013126. doi:10.1006\/geno.1994.1588. PMID\u00a07896265.Zhang Q, Didonato JA, Karin M, McKeithan TW (June 1994). “BCL3 encodes a nuclear protein which can alter the subcellular location of NF-kappa B proteins”. Molecular and Cellular Biology. 14 (6): 3915\u20133926. doi:10.1128\/MCB.14.6.3915. PMC\u00a0358758. PMID\u00a08196632.Fujita T, Nolan GP, Liou HC, Scott ML, Baltimore D (July 1993). “The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers”. Genes & Development. 7 (7B): 1354\u20131363. doi:10.1101\/gad.7.7b.1354. PMID\u00a08330739.Naumann M, Wulczyn FG, Scheidereit C (January 1993). “The NF-kappa B precursor p105 and the proto-oncogene product Bcl-3 are I kappa B molecules and control nuclear translocation of NF-kappa B”. The EMBO Journal. 12 (1): 213\u2013222. doi:10.1002\/j.1460-2075.1993.tb05647.x. PMC\u00a0413194. PMID\u00a08428580.Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, Siebenlist U (March 1993). “The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers”. Cell. 72 (5): 729\u2013739. doi:10.1016\/0092-8674(93)90401-B. PMID\u00a08453667.Nolan GP, Fujita T, Bhatia K, Huppi C, Liou HC, Scott ML, Baltimore D (June 1993). “The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner”. Molecular and Cellular Biology. 13 (6): 3557\u20133566. doi:10.1128\/MCB.13.6.3557. PMC\u00a0359825. PMID\u00a08497270.Watanabe N, Iwamura T, Shinoda T, Fujita T (June 1997). “Regulation of NFKB1 proteins by the candidate oncoprotein BCL-3: generation of NF-kappaB homodimers from the cytoplasmic pool of p50-p105 and nuclear translocation”. The EMBO Journal. 16 (12): 3609\u20133620. doi:10.1093\/emboj\/16.12.3609. PMC\u00a01169985. PMID\u00a09218802.Bundy DL, McKeithan TW (December 1997). “Diverse effects of BCL3 phosphorylation on its modulation of NF-kappaB p52 homodimer binding to DNA”. The Journal of Biological Chemistry. 272 (52): 33132\u201333139. doi:10.1074\/jbc.272.52.33132. PMID\u00a09407099.Weyrich AS, Dixon DA, Pabla R, Elstad MR, McIntyre TM, Prescott SM, Zimmerman GA (May 1998). “Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets”. Proceedings of the National Academy of Sciences of the United States of America. 95 (10): 5556\u20135561. Bibcode:1998PNAS…95.5556W. doi:10.1073\/pnas.95.10.5556. PMC\u00a020416. PMID\u00a09576921.Na SY, Choi HS, Kim JW, Na DS, Lee JW (November 1998). “Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor”. The Journal of Biological Chemistry. 273 (47): 30933\u201330938. doi:10.1074\/jbc.273.47.30933. PMID\u00a09812988.Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG,  et\u00a0al. (June 1999). “The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB\/Rel and nuclear co-regulators”. Oncogene. 18 (22): 3316\u20133323. doi:10.1038\/sj.onc.1202717. PMID\u00a010362352.Na SY, Choi JE, Kim HJ, Jhun BH, Lee YC, Lee JW (October 1999). “Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation”. The Journal of Biological Chemistry. 274 (40): 28491\u201328496. doi:10.1074\/jbc.274.40.28491. PMID\u00a010497212.Neumann M, Fries H, Scheicher C, Keikavoussi P, Kolb-M\u00e4urer A, Br\u00f6cker E,  et\u00a0al. (January 2000). “Differential expression of Rel\/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells”. Blood. 95 (1): 277\u2013285. doi:10.1182\/blood.V95.1.277. PMID\u00a010607713.Brasier AR, Lu M, Hai T, Lu Y, Boldogh I (August 2001). “NF-kappa B-inducible BCL-3 expression is an autoregulatory loop controlling nuclear p50\/NF-kappa B1 residence”. The Journal of Biological Chemistry. 276 (34): 32080\u201332093. doi:10.1074\/jbc.M102949200. PMID\u00a011387332.External links[edit]PDB gallery1k1a: Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family1k1b: Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family  "},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/bcl3-wikipedia\/#breadcrumbitem","name":"BCL3 – Wikipedia"}}]}]