BCL6

The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

B Cell CLL/Lymphoma 6

Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4+ T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53-dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation.

Actin cytoskeleton organization Source: Ensembl
B cell differentiation Source: Ensembl
Cell morphogenesis Source: Ensembl
Cellular response to DNA damage stimulus Source: UniProtKB
Cytokine-mediated signaling pathway Source: Reactome
Erythrocyte development Source: Ensembl
Germinal center formation Source: Ensembl
Inflammatory response Source: UniProtKB-KW
Negative regulation of B cell apoptotic process Source: UniProtKB
Negative regulation of cell growth Source: UniProtKB
Negative regulation of cell-matrix adhesion Source: Ensembl
Negative regulation of cell population proliferation Source: Ensembl
Negative regulation of cellular senescence Source: Ensembl
Negative regulation of isotype switching to IgE isotypes Source: Ensembl
Negative regulation of mast cell cytokine production Source: Ensembl
Negative regulation of mitotic cell cycle DNA replication Source: UniProtKB
Negative regulation of Notch signaling pathway Source: Ensembl
Negative regulation of Rho protein signal transduction Source: Ensembl
Negative regulation of T-helper 2 cell differentiation Source: Ensembl
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of B cell proliferation Source: Ensembl
Positive regulation of cellular component movement Source: Ensembl
Positive regulation of histone deacetylation Source: Ensembl
Positive regulation of neuron differentiation Source: Ensembl
Positive regulation of regulatory T cell differentiation Source: ARUK-UCL
Protein localization Source: Ensembl
Regulation of apoptotic process Source: Reactome
Regulation of cell differentiation Source: GO_Central
Regulation of cell population proliferation Source: GO_Central
Regulation of cytokine production Source: GO_Central
Regulation of germinal center formation Source: UniProtKB
Regulation of GTPase activity Source: Ensembl
Regulation of immune response Source: UniProtKB
Regulation of immune system process Source: GO_Central
Regulation of inflammatory response Source: GO_Central
Regulation of memory T cell differentiation Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Rho protein signal transduction Source: Ensembl
Spermatogenesis Source: Ensembl
Type 2 immune response Source: GO_Central

Nucleus

Chromosomal aberrations involving BCL6 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-cell lymphomas and 5 to 10% of follicular lymphomas are associated with chromosomal translocations that deregulate expression of BCL6 by juxtaposing heterologous promoters to the BCL6 coding domain (PubMed:10469447, PubMed:10753856, PubMed:12414651, PubMed:11821949). Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with immunoglobulin gene regions (PubMed:11821949). Translocation t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region (PubMed:10753856). Translocation t(3;6)(q27;p21) with Histone H4 (PubMed:12414651). Translocation t(3;16)(q27;p11) with IL21R. Translocation t(3;13)(q27;q14) with LCP1 (PubMed:10469447).
A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.
A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.

Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-333 and Ser-343. Phosphorylated by ATM in response to genotoxic stress. Phosphorylation induces its degradation by ubiquitin/proteasome pathway.
Polyubiquitinated (PubMed:9649500, PubMed:22113614, PubMed:30190310). Polyubiquitinated by SCF(FBXO11), leading to its degradation by the proteasome (PubMed:22113614). Ubiquitinated by the SCF(FBXL17) complex, leading to its degradation by the proteaseome: ubiquitination by the SCF(FBXL17) complex takes place when aberrant BTB domain dimers are formed (PubMed:30190310).
Acetylated at Lys-379 by EP300 which inhibits the interaction with NuRD complex and the transcriptional repressor function. Deacetylated by HDAC- and SIR2-dependent pathways.