Biology:BCL3
Generic protein structure example |
B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.[1][2]
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.[3]
Like BCL2, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.
Interactions
BCL3 has been shown to interact with:
- BARD1,[4]
- C-Fos,[5]
- C-jun,[5]
- C22orf25,[6]
- COPS5,[4]
- EP300,[5]
- HTATIP,[4]
- NFKB1,[7][8][9]
- NFKB2,[7][10]
- PIR,[4] and
- NR2B1.[11]
Clinical significance
Genetic variations in BCL3 gene have been associated with late-onset Alzheimer's disease (LOAD) and chronic lymphocytic leukemia. β-amyloid accumulation in neurons of Alzheimer's patients results in activation of NF-κB, which induces BCL3 expression.[12] Increased expression of BCL3 has been observed in the brains of patients with LOAD.[13]
References
- ↑ "Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-kappa B". Nature 358 (6387): 597–599. August 1992. doi:10.1038/358597a0. PMID 1501714. Bibcode: 1992Natur.358..597W.
- ↑ "The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control". Cell 60 (6): 991–997. March 1990. doi:10.1016/0092-8674(90)90347-H. PMID 2180580.
- ↑ "Entrez Gene: BCL3 B-cell CLL/lymphoma 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=602.
- ↑ 4.0 4.1 4.2 4.3 "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators". Oncogene 18 (22): 3316–3323. June 1999. doi:10.1038/sj.onc.1202717. PMID 10362352.
- ↑ 5.0 5.1 5.2 "Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation". The Journal of Biological Chemistry 274 (40): 28491–28496. October 1999. doi:10.1074/jbc.274.40.28491. PMID 10497212.
- ↑ "Molecular Interaction Database". http://mint.bio.uniroma2.it/mint/Welcome.do.
- ↑ 7.0 7.1 "Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma". Cancer Research 63 (23): 8293–8301. December 2003. PMID 14678988.
- ↑ "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): 213–222. January 1993. doi:10.1002/j.1460-2075.1993.tb05647.x. PMID 8428580.
- ↑ "NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of Bcl-3-p50 complexes". The EMBO Journal 18 (17): 4766–4778. September 1999. doi:10.1093/emboj/18.17.4766. PMID 10469655.
- ↑ "The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers". Cell 72 (5): 729–739. March 1993. doi:10.1016/0092-8674(93)90401-b. PMID 8453667.
- ↑ "Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor". The Journal of Biological Chemistry 273 (47): 30933–30938. November 1998. doi:10.1074/jbc.273.47.30933. PMID 9812988.
- ↑ "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. May 2017. doi:10.1186/s12920-017-0267-0. PMID 28589856.
- ↑ "A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease". Nature Genetics 53 (9): 1276–1282. September 2021. doi:10.1038/s41588-021-00921-z. ISSN 1061-4036. PMID 34493870. https://research.vu.nl/en/publications/61f01aa9-6dc7-4213-be2a-d3fe622db488.
Further reading
- "The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-kappa B-mediated inhibition". Nature 359 (6393): 339–342. September 1992. doi:10.1038/359339a0. PMID 1406939. Bibcode: 1992Natur.359..339F. https://zenodo.org/record/1233131.
- "Mouse bcl-3: cDNA structure, mapping and stage-dependent expression in B lymphocytes". Oncogene 6 (9): 1569–1573. September 1991. PMID 1923524.
- "Sequences of human immunoglobulin switch regions: implications for recombination and transcription". Nucleic Acids Research 18 (24): 7305–7316. December 1990. doi:10.1093/nar/18.24.7305. PMID 2124350.
- "Cloning and sequencing of a t(14;19) breakpoint that involves the C mu switch region". Genes, Chromosomes & Cancer 8 (1): 60–62. September 1993. doi:10.1002/gcc.2870080110. PMID 7691160.
- "Genomic structure of the candidate proto-oncogene BCL3". Genomics 24 (1): 120–126. November 1994. doi:10.1006/geno.1994.1588. PMID 7896265.
- "BCL3 encodes a nuclear protein which can alter the subcellular location of NF-kappa B proteins". Molecular and Cellular Biology 14 (6): 3915–3926. June 1994. doi:10.1128/MCB.14.6.3915. PMID 8196632.
- "The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-kappa B p50 homodimers". Genes & Development 7 (7B): 1354–1363. July 1993. doi:10.1101/gad.7.7b.1354. PMID 8330739.
- "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): 213–222. January 1993. doi:10.1002/j.1460-2075.1993.tb05647.x. PMID 8428580.
- "The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers". Cell 72 (5): 729–739. March 1993. doi:10.1016/0092-8674(93)90401-B. PMID 8453667.
- "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): 3557–3566. June 1993. doi:10.1128/MCB.13.6.3557. PMID 8497270.
- "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): 3609–3620. June 1997. doi:10.1093/emboj/16.12.3609. PMID 9218802.
- "Diverse effects of BCL3 phosphorylation on its modulation of NF-kappaB p52 homodimer binding to DNA". The Journal of Biological Chemistry 272 (52): 33132–33139. December 1997. doi:10.1074/jbc.272.52.33132. PMID 9407099.
- "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): 5556–5561. May 1998. doi:10.1073/pnas.95.10.5556. PMID 9576921. Bibcode: 1998PNAS...95.5556W.
- "Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor". The Journal of Biological Chemistry 273 (47): 30933–30938. November 1998. doi:10.1074/jbc.273.47.30933. PMID 9812988.
- "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators". Oncogene 18 (22): 3316–3323. June 1999. doi:10.1038/sj.onc.1202717. PMID 10362352.
- "Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation". The Journal of Biological Chemistry 274 (40): 28491–28496. October 1999. doi:10.1074/jbc.274.40.28491. PMID 10497212.
- "Differential expression of Rel/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells". Blood 95 (1): 277–285. January 2000. doi:10.1182/blood.V95.1.277. PMID 10607713.
- "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): 32080–32093. August 2001. doi:10.1074/jbc.M102949200. PMID 11387332.
External links
- FactorBook BCL3
- Human BCL3 genome location and BCL3 gene details page in the UCSC Genome Browser.