Disease relevance of BCL3

• In the patient's leukemia cells, the truncated MYC gene was highly expressed under the influence of BCL3 regulatory elements, leading to an aggressive B-cell leukemia that presumably had been derived from an indolent lymphoma carrying a rearranged BCL2 gene [1].
• We established a real-time reverse transcriptase-mediated polymerase chain reaction assay to measure the BCL3 mRNA level and found a predominant level of BCL3 expression in t(2;5)(+) ALCL; the levels of cell lines and clinical materials were comparable to or higher than that of a B-cell chronic lymphocytic leukemia carrying t(14;19)(q32;q13) [2].
• High-level expression of BCL3 differentiates t(2;5)(p23;q35)-positive anaplastic large cell lymphoma from Hodgkin disease [2].
• Nonsyndromic cleft lip with or without cleft palate: evidence of linkage to BCL3 in 17 multigenerational families [3].
• As an initial step in analyzing transcriptional responses of BCL3 in T cells, we have identified candidate regulatory regions within the locus through their evolutionary conservation and by analysis of DNase hypersensitivity [4].

High impact information on BCL3

• The protein Bcl-3 contains seven so-called ankyrin repeats [5].
• One of these is the putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia [6].
• GSK3-mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity [7].
• We expressed BCL-3 ectopically in pro-B cell lines and found that these cells exhibited a dramatic increase in nuclear kappaB motif binding activity of p50 homodimers containing BCL-3 in the complex [8].
• Nonsyndromic cleft lip with or without cleft palate: new BCL3 information [9].

Chemical compound and disease context of BCL3

• In luciferase reporter gene constructs transiently transfected into the Jurkat T cell line, the HS3 enhancer can cooperate not only with the BCL3 promoter, but also with an exogenous promoter from herpes simplex thymidine kinase [4].
• We assessed BCL-3 expression in 353 cases of non-Hodgkin lymphoma and Hodgkin lymphoma using formalin-fixed, paraffin-embedded tissue specimens, a monoclonal antibody specific for BCL-3, and immunohistochemical methods [10].

Biological context of BCL3

• The BCL3 locus was mapped to chromosome 17 band q22 [1].
• We compared gene expression profiles of 4 ALCL (Karpas 299, SU-DHL-1, DEL, SR-786) and 3 HD cell lines and found that BCL3, which encodes a nuclear protein belonging to the I kappa B family of inhibitors of nuclear factor-kappa B (NF-kappa B) transcriptional factors, was expressed at higher levels in ALCL than HD [2].
• The BCL3 gene contains 2 cytosine-guanine dinucleotide (CpG) islands, and the intragenic 3' CpG was entirely demethylated in SU-DHL-1 and DEL [2].
• Immunoglobulin gene chromosomal translocations are rare in CLL and involve a distinct subset of genes including BCL3, BCL11A and CCND2 [11].
• Genomic structure of the candidate proto-oncogene BCL3 [12].

Anatomical context of BCL3

• We found BCL3 transcribed as a message of 1.7 kilobases in many hematopoietic cell lines representing all hematopoietic lineages [1].
• The adjuvant-derived signals provided to T cells are poorly understood, but recent work has identified BCL3 as the gene, of those tested, with the greatest differential transcriptional response to adjuvant administration in vivo [4].
• Furthermore, microinjection of Bcl3 expression vector into Rat-1 fibroblast cells significantly enhanced DNA synthesis and expression of c-jun, one of the cellular target genes of AP-1 [13].
• In addition, anti-HA antibody co-precipitated c-Jun from HeLa cells co-expressing c-Jun and HA-tagged Bcl3, consistent with the idea that Bcl3 directly associates with AP-1 in vivo [13].
• These same signaling pathways were shown to initiate antiapoptotic events and promote eosinophil survival, including up-regulation of BCL2 and BCL3 [14].

Associations of BCL3 with chemical compounds

• PCR-amplified products using four microsatellite markers, D19S178, BCL3, APOC2[007/008] and APOC2[AC1/AC2] located in 19q13.2, were separated by 8% polyacrylamide gel electrophoresis [15].
• Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor [16].
• Herein, we show that a distinct IkappaB protein Bcl3 also interacts with RXR, as shown in the yeast two-hybrid tests and glutathione S-transferase pull-down assays [16].
• Moreover, the IL-12-induced STAT4 engenders greater clonal expansion of the Ag-activated CD8 cells by regulating the expression of the transcriptional factor Bcl3- and Bcl2-related genes that promote survival of Ag-activated CD8 cells [17].

Physical interactions of BCL3

• BCL3 protein acts as an I kappa B in that it can specifically inhibit the DNA binding of NF-kappa B factors [18].
• Here we have identified and characterized BCL-3-binding protein (B3BP) as a protein interacting specifically with the bcl-3 gene product (BCL-3) by a yeast two-hybrid screen [19].
• Up-regulation of Cyclin D1 by HBx Is Mediated by NF-{kappa}B2/BCL3 Complex through {kappa}B Site of Cyclin D1 Promoter [20].
• The ankyrin repeat domain of BCL3 interacted with TORC3 [21].

Regulatory relationships of BCL3

• NF-kappa B regulates BCL3 transcription in T lymphocytes through an intronic enhancer [4].
• In addition, coexpression of SRC-1 but not p300 further stimulated the Bcl3-mediated enhancement of the 9-cis-RA-induced transactivations of RXR [16].
• Either inhibition of Akt1 or depletion of Bcl3 blocks Bcl10 nuclear translocation [22].
• BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription [23].
• A comparison by real-time polymerase chain reaction assay revealed that t(2;5)+ ALCL expresses a high level of BCL3 messenger RNA relative to the levels expressed in other hematologic tumors, and the level in ALCL is comparable to or even higher than that in t(14;19)+ B-CLL [24].

Other interactions of BCL3

• Interestingly, we observed an interaction between the maternal MTHFR and offspring's BCL3 genotypes (OR: 2.3; 95% CI: 1.1-4.8; P=0.03) but not with the offspring's TGFA genotypes [25].
• Four of them showed significant deviations from Hardy-Weinberg expectations in controls, according to the exact test (D4S192, BCL3, F13A1, and D6S89) [26].
• Involvement of the BCL1, BCL2, and BCL3 genes has been reported, but the numbers are low and the cases tend to be atypical [27].
• The other partners were 19q13 (BCL3), 6p25 (MUM1/IRF4), 1q36, and chromosome 8 identified in one patient each [28].
• Significant linkage to 6p23 (EDN1) or 19q13 (BCL3) could be achieved using parametric models with reduced penetrance [29].

Analytical, diagnostic and therapeutic context of BCL3

• Southern blotting and fluorescence in situ hybridization disclosed that the BCL3 gene copies were amplified in SU-DHL-1, whereas Karpas 299 carried 4 BCL3 gene loci [2].
• Northern and Western blotting analyses confirmed the high-level expression of BCL3 in ALCL at both mRNA and protein levels [2].
• Further immunofluorescence experiments showed that a mutant p50, lacking a nuclear localization signal and restricted to the cytoplasm, is brought into the nucleus in the presence of BCL3 [18].
• To study BCL3 function, we have used gel shift analysis and tagged protein and tagged DNA coprecipitation analyses [30].
• Sequence analysis of the BCL3 gene locus revealed four potential signal transducer and activator of transcription (Stat) binding sites within two conserved intronic enhancers regions: one located within enhancer HS3 and three within HS4 [23].

References