DegronMD - P41182(BCL6)

FUNCTION: 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. {ECO:0000269|PubMed:10981963, ECO:0000269|PubMed:12402037, ECO:0000269|PubMed:12414651, ECO:0000269|PubMed:12504096, ECO:0000269|PubMed:15454082, ECO:0000269|PubMed:15577913, ECO:0000269|PubMed:16142238, ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:18280243, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:23166356, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:9649500}. View more >>

GO - Biological processes (BP): actin cytoskeleton organization [GO:0030036]; B cell differentiation [GO:0030183]; cell morphogenesis [GO:0000902]; cellular response to DNA damage stimulus [GO:0006974]; erythrocyte development [GO:0048821]; germinal center formation [GO:0002467]; inflammatory response [GO:0006954]; negative regulation of B cell apoptotic process [GO:0002903]; negative regulation of cell growth [GO:0030308]; negative regulation of cell-matrix adhesion [GO:0001953]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of cellular senescence [GO:2000773]; negative regulation of isotype switching to IgE isotypes [GO:0048294]; negative regulation of mast cell cytokine production [GO:0032764]; negative regulation of mitotic cell cycle DNA replication [GO:1903464]; negative regulation of Notch signaling pathway [GO:0045746]; negative regulation of Rho protein signal transduction [GO:0035024]; negative regulation of T-helper 2 cell differentiation [GO:0045629]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of apoptotic process [GO:0043065]; positive regulation of B cell proliferation [GO:0030890]; positive regulation of cellular component movement [GO:0051272]; positive regulation of histone deacetylation [GO:0031065]; positive regulation of neuron differentiation [GO:0045666]; positive regulation of regulatory T cell differentiation [GO:0045591]; protein localization [GO:0008104]; regulation of cell differentiation [GO:0045595]; regulation of cell population proliferation [GO:0042127]; regulation of cytokine production [GO:0001817]; regulation of germinal center formation [GO:0002634]; regulation of GTPase activity [GO:0043087]; regulation of immune response [GO:0050776]; regulation of immune system process [GO:0002682]; regulation of inflammatory response [GO:0050727]; regulation of memory T cell differentiation [GO:0043380]; regulation of transcription by RNA polymerase II [GO:0006357]; Rho protein signal transduction [GO:0007266]; spermatogenesis [GO:0007283]; type 2 immune response [GO:0042092] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A313T	TCGA-2W-A8YY	CESC	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation altering degron motif	0.6028
p.A313T	DO223732	CESC	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation altering degron motif	0.6028
p.M470I	TCGA-2Z-A9J2	KIRP	TCGA	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.1111
p.M470I	DO219650	KIRP	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.1111
p.D310G	TCGA-AP-A056	UCEC	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.2778
p.D310G	DO43971	UCEC	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.2778
p.E311D	TCGA-AP-A0LM	UCEC	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.3056
p.E311D	DO43306	UCEC	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.3056
p.I449V	TCGA-BP-5190	KIRC	TCGA	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.0833
p.I449V	DO17937	KIRC	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.0833
p.E302D	TCGA-BS-A0UJ	UCEC	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.0556
p.E302D	DO42745	UCEC	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.0556
p.R459H	TCGA-D1-A16X	UCEC	TCGA	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.7133
p.R459H	TCGA-D1-A174	UCEC	TCGA	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.7133
p.R459H	DO234459	ESAD	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.7133
p.R459H	DO40900	UCEC	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.7133
p.R459H	DO41799	UCEC	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.7133
p.L314V	TCGA-DI-A2QY	UCEC	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation altering degron motif	0.5654
p.L314V	DO42031	UCEC	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation altering degron motif	0.5654
p.R452M	TCGA-DU-6392	LGG	TCGA	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.1667
p.R452M	DO22237	LGG	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.1667
p.R459C	TCGA-EE-A29V	SKCM	TCGA	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.719
p.R459C	DO222843	MELA	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.719
p.R459C	DO38006	SKCM	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.719
p.A321T	TCGA-EJ-7783	PRAD	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.2222
p.A321T	DO36362	PRAD	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.2222
p.A313V	TCGA-FW-A3R5	SKCM	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation altering degron motif	0.5825
p.A313V	DO37406	SKCM	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation altering degron motif	0.5825
p.K326N	TCGA-UL-AAZ6	BRCA	TCGA	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation substituting flanking lysine	0.1944
p.K326N	DO219644	BRCA	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation substituting flanking lysine	0.1944
p.M454I	DO234371	ESAD	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.2222
p.R325W	DO222482	ESCA	ICGC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.1111
p.P458H	DO228952	LICA	ICGC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.7694
p.M454T	SIDM00251	Gastric Carcinoma	GDSC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.2222
p.M454T	ACH-000949	Gastric Cancer	CCLE	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.2222
p.M454T	TGBC11TKB	stomach	COSMIC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.2222
p.E463K	SIDM01323	Oral Cavity Carcinoma	GDSC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.3056
p.E463K	ACH-000732	Head and Neck Cancer	CCLE	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation rewiring degron network	0.3056
p.P458S	ACH-000824	Esophageal Cancer	CCLE	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.6752
p.P458S	KYSE-510	oesophagus	COSMIC	PRSSS	DEG_SPOP_SBC_1	458:462	Mutation altering degron motif	0.6752
p.A321V	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	IALHFE	LIG_APCC_ABBA_1	312:317	Mutation rewiring degron network	0.2222

Kaplan plot for BCL6 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

BCL6

UniProt ID: P41182

Entrez ID: 604

Protein name: B-cell lymphoma 6 protein (BCL-6) (B-cell lymphoma 5 protein) (BCL-5) (Protein LAZ-3) (Zinc finger and BTB domain-containing protein 27) (Zinc finger protein 51)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for BCL6 in