BCL6 - B-cell lymphoma 6 protein - human protein (Function)
 
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Protein
Gene
References

 
BCL6 »  B-cell lymphoma 6 protein
 
Gene name:  BCL6
Entry whose protein(s) existence is based on evidence at protein level
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1 69 2
GENE REF ISO

Function

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Overview 
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.  
14
  • CuratedUniProtKB
GO molecular function 
Chromatin bindingdefinition[GO:0003682]  
1
  • IDAMGI
Chromatin DNA bindingdefinition[GO:0031490] silver  
  • IEAOrtholog Compara
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
4
  • IPIUniProtKB
  • IPIIntAct
Sequence-specific DNA bindingdefinition[GO:0043565]  
1
  • IDAUniProtKB
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
1
  • IMPUniProtKB
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036] silver  
  • IEAOrtholog Compara
B cell differentiationdefinition[GO:0030183] silver  
  • IEAOrtholog Compara
Cell morphogenesisdefinition[GO:0000902] silver  
  • IEAOrtholog Compara
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • IDAUniProtKB
Erythrocyte developmentdefinition[GO:0048821] silver  
  • IEAOrtholog Compara
Germinal center formationdefinition[GO:0002467] silver  
  • IEAOrtholog Compara
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Negative regulation of B cell apoptotic processdefinition[GO:0002903]  
1
  • NASUniProtKB
Negative regulation of cell growthdefinition[GO:0030308]  
1
  • IDAUniProtKB
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
  • IEAOrtholog Compara
Negative regulation of cell-matrix adhesiondefinition[GO:0001953] silver  
  • IEAOrtholog Compara
Negative regulation of isotype switching to IgE isotypesdefinition[GO:0048294] silver  
  • IEAOrtholog Compara
Negative regulation of mast cell cytokine productiondefinition[GO:0032764] silver  
  • IEAOrtholog Compara
Negative regulation of Rho protein signal transductiondefinition[GO:0035024] silver  
  • IEAOrtholog Compara
Negative regulation of T-helper 2 cell differentiationdefinition[GO:0045629] silver  
  • IEAOrtholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122]  
2
  • IDAUniProtKB
  • IDAMGI
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
2
  • IMPUniProtKB
Negative regulation of type 2 immune responsedefinition[GO:0002829] silver  
  • IEAOrtholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • IDAUniProtKB
Positive regulation of B cell proliferationdefinition[GO:0030890] silver  
  • IEAOrtholog Compara
Positive regulation of cellular component movementdefinition[GO:0051272] silver  
  • IEAOrtholog Compara
Protein import into nucleus, translocationdefinition[GO:0000060]  
1
  • IGIUniProtKB
Regulation of germinal center formationdefinition[GO:0002634]  
1
  • NASUniProtKB
Regulation of immune responsedefinition[GO:0050776]  
1
  • NASUniProtKB
Regulation of inflammatory responsedefinition[GO:0050727] silver  
  • IEAOrtholog Compara
Regulation of memory T cell differentiationdefinition[GO:0043380] silver  
  • IEAOrtholog Compara
Regulation of Rho GTPase activitydefinition[GO:0032319] silver  
  • IEAOrtholog Compara
Rho protein signal transductiondefinition[GO:0007266] silver  
  • IEAOrtholog Compara
Spermatogenesisdefinition[GO:0007283] silver  
  • IEAOrtholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Type 2 immune responsedefinition[GO:0042092] silver  
  • IEAOrtholog Compara
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Repressor  definition   [KW-0678]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: BCL6
GenomeRNAi: 604
PRO: PR:P41182