BCL6 - B-cell lymphoma 6 protein - human protein (Function)
 
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BCL6 »  B-cell lymphoma 6 protein  (BCL-6)
 
Protein also known as:  Zinc finger and BTB domain-containing protein 27.
Gene name:  BCL6
Entry whose protein(s) existence is based on evidence at protein level
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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.  
15
  • UniProtKB
GO molecular function 
Chromatin bindingdefinition[GO:0003682]  
1
  • MGI
Chromatin DNA bindingdefinition[GO:0031490] silver  
1
  • Ortholog Compara
Metal ion bindingdefinition[GO:0046872]  
1
  • UniProtKB KW
Protein bindingdefinition[GO:0005515]  
5
  • IntAct
  • UniProtKB
RNA polymerase II regulatory region sequence-specific DNA bindingdefinition[GO:0000977] silver  
1
  • Ortholog Compara
RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcriptiondefinition[GO:0001227] silver  
1
  • Ortholog Compara
Sequence-specific DNA bindingdefinition[GO:0043565]  
1
  • UniProtKB
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
1
  • UniProtKB
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036] silver  
1
  • Ortholog Compara
B cell differentiationdefinition[GO:0030183] silver  
1
  • Ortholog Compara
Cell morphogenesisdefinition[GO:0000902] silver  
1
  • Ortholog Compara
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • UniProtKB
Erythrocyte developmentdefinition[GO:0048821] silver  
1
  • Ortholog Compara
Germinal center formationdefinition[GO:0002467] silver  
1
  • Ortholog Compara
Inflammatory responsedefinition[GO:0006954]  
1
  • UniProtKB KW
Negative regulation of B cell apoptotic processdefinition[GO:0002903]  
1
  • UniProtKB
Negative regulation of cell growthdefinition[GO:0030308]  
1
  • UniProtKB
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
1
  • Ortholog Compara
Negative regulation of cell-matrix adhesiondefinition[GO:0001953] silver  
1
  • Ortholog Compara
Negative regulation of cellular senescencedefinition[GO:2000773] silver  
1
  • Ortholog Compara
Negative regulation of isotype switching to IgE isotypesdefinition[GO:0048294] silver  
1
  • Ortholog Compara
Negative regulation of mast cell cytokine productiondefinition[GO:0032764] silver  
1
  • Ortholog Compara
Negative regulation of Notch signaling pathwaydefinition[GO:0045746] silver  
1
  • Ortholog Compara
Negative regulation of Rho protein signal transductiondefinition[GO:0035024] silver  
1
  • Ortholog Compara
Negative regulation of T-helper 2 cell differentiationdefinition[GO:0045629] silver  
1
  • Ortholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122]  
2
  • UniProtKB
  • MGI
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
2
  • UniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • UniProtKB
Positive regulation of B cell proliferationdefinition[GO:0030890] silver  
1
  • Ortholog Compara
Positive regulation of cellular component movementdefinition[GO:0051272] silver  
1
  • Ortholog Compara
Positive regulation of histone deacetylationdefinition[GO:0031065] silver  
1
  • Ortholog Compara
Positive regulation of neuron differentiationdefinition[GO:0045666] silver  
1
  • Ortholog Compara
Protein import into nucleus, translocationdefinition[GO:0000060]  
1
  • UniProtKB
Regulation of germinal center formationdefinition[GO:0002634]  
1
  • UniProtKB
Regulation of immune responsedefinition[GO:0050776]  
1
  • UniProtKB
Regulation of inflammatory responsedefinition[GO:0050727] silver  
1
  • Ortholog Compara
Regulation of memory T cell differentiationdefinition[GO:0043380] silver  
1
  • Ortholog Compara
Rho protein signal transductiondefinition[GO:0007266] silver  
1
  • Ortholog Compara
Spermatogenesisdefinition[GO:0007283] silver  
1
  • Ortholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Type 2 immune responsedefinition[GO:0042092] silver  
1
  • Ortholog 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