BCL6

BCL6
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1R28, 1R29, 1R2B, 2EN2, 2EOS, 2LCE, 2YRM, 3BIM, 3E4U, 3LBZ, 4CP3, 4U2M
Identifiers
Aliases	BCL6, BCL5, BCL6A, LAZ3, ZBTB27, ZNF51, B-cell CLL/lymphoma 6, B cell CLL/lymphoma 6, transcription repressor, BCL6 transcription repressor
External IDs	OMIM: 109565 MGI: 107187 HomoloGene: 7640 GeneCards: BCL6
Gene location (Human)
Chr.	Chromosome 3 (human)[1]
End	187,745,725 bp[1]
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)[2]
End	23,988,852 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• sequence-specific DNA binding; • DNA binding; • RNA polymerase II regulatory region sequence-specific DNA binding; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • intronic transcription regulatory region sequence-specific DNA binding; • chromatin binding; • metal ion binding; • GO:0001948 protein binding; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • nucleic acid binding; • chromatin DNA binding; • identical protein binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	• replication fork; • cell nucleus; • nucleoplasm; • Golgi apparatus;
Biological process	• regulation of germinal center formation; • positive regulation of histone deacetylation; • negative regulation of T-helper 2 cell differentiation; • protein localization; • negative regulation of mast cell cytokine production; • regulation of transcription, DNA-templated; • immune system process; • GO:0043087, GO:0032313, GO:0032319, GO:0032314, GO:0043088 regulation of GTPase activity; • regulation of transcription from RNA polymerase II promoter; • negative regulation of cell differentiation; • germinal center formation; • negative regulation of Rho protein signal transduction; • negative regulation of isotype switching to IgE isotypes; • negative regulation of apoptotic process; • negative regulation of transcription from RNA polymerase II promoter; • transcription, DNA-templated; • type 2 immune response; • cellular response to DNA damage stimulus; • negative regulation of cell-matrix adhesion; • regulation of cell proliferation; • positive regulation of B cell proliferation; • negative regulation of cell growth; • Rho protein signal transduction; • cell morphogenesis; • spermatogenesis; • regulation of memory T cell differentiation; • positive regulation of neuron differentiation; • regulation of inflammatory response; • regulation of immune response; • positive regulation of apoptotic process; • negative regulation of type 2 immune response; • negative regulation of B cell apoptotic process; • positive regulation of cellular component movement; • B cell differentiation; • inflammatory response; • negative regulation of transcription, DNA-templated; • actin cytoskeleton organization; • negative regulation of cell proliferation; • negative regulation of Notch signaling pathway; • erythrocyte development; • negative regulation of cellular senescence; • regulation of apoptotic process; • negative regulation of mitotic cell cycle DNA replication; • positive regulation of regulatory T cell differentiation; • cytokine-mediated signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	604
	12053
	ENSG00000113916
	ENSMUSG00000022508
	P41182
	P41183
	NM_001130845; NM_001134738; NM_001706; NM_138931
	NM_009744; NM_001348026
	NP_001124317; NP_001128210; NP_001697
	NP_001334955; NP_033874
	Wikidata
View/Edit Human	View/Edit Mouse

B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.[5] Like BCL2, BCL3, BCL5, BCL7A, BCL9 and BCL10, it has clinical significance in lymphoma.

Function

The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain. This protein acts as a sequence-specific repressor of transcription and has been shown to modulate the STAT-dependent Interleukin 4 (IL-4) responses of B cells. This protein can interact with several corepressor complexes to inhibit transcription. This gene is found to be frequently translocated and hypermutated in diffuse large B cell lymphoma (DLBCL)[6][7][8] and contributes to the pathogenesis of DLBCL. An exon 7 skipping splice variant encodes a shorter form of the protein which lacks the first two zinc fingers of the DNA binding domain.[9]

Physiologically, BCL6 is a master transcription factor which leads the differentiation of naive helper T cells in Follicular Helper T cells (TFH cells).[10] Its action is negatively regulated by the gene PRDM1 encoding the transcription factor Blimp-1.[11]

Diagnostic utility

The presence of BCL6 can be demonstrated in tissue sections using immunohistochemistry. It is exclusively present in the B-cells of both healthy and neoplastic germinal centres. It therefore demonstrates both reactive hyperplasia in lymph nodes and a range of lymphomas derived from follicular B-cells, such as Burkitt's lymphoma, follicular lymphoma and the nodular lymphocyte predominant subtype of Hodgkin's disease. It is often used together with antibodies to Bcl-2 antigen to distinguish neoplastic follicles from those found in benign hyperplasia, for which Bcl-2 is negative.[12]

Interactions

BCL6 has been shown to interact with

References

GRCh38: Ensembl release 89: ENSG00000113916 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000022508 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51)".
Ye BH, Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R (October 1993). "Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma". Science. 262 (5134): 747–50. Bibcode:1993Sci...262..747Y. doi:10.1126/science.8235596. PMID 8235596.
Kerckaert JP, Deweindt C, Tilly H, Quief S, Lecocq G, Bastard C (September 1993). "LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas". Nature Genetics. 5 (1): 66–70. doi:10.1038/ng0993-66. PMID 8220427. S2CID 12575122.
Migliazza A, Martinotti S, Chen W, Fusco C, Ye BH, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R (December 1995). "Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma". Proceedings of the National Academy of Sciences of the United States of America. 92 (26): 12520–4. Bibcode:1995PNAS...9212520M. doi:10.1073/pnas.92.26.12520. PMC 40389. PMID 8618933.
Shen Y, Ge B, Ramachandrareddy H, McKeithan T, Chan WC (October 2008). "Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor". Biochemical and Biophysical Research Communications. 375 (2): 190–3. doi:10.1016/j.bbrc.2008.07.116. PMC 2573862. PMID 18675787.
Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C (August 2009). "Bcl6 mediates the development of T follicular helper cells". Science. 325 (5943): 1001–5. Bibcode:2009Sci...325.1001N. doi:10.1126/science.1176676. PMC 2857334. PMID 19628815.
Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent AL, Craft J, Crotty S (August 2009). "Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation". Science. 325 (5943): 1006–10. Bibcode:2009Sci...325.1006J. doi:10.1126/science.1175870. PMC 2766560. PMID 19608860.
Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2nd ed.). Greenwich Medical Media, Ltd. p. 29. ISBN 978-1-84110-100-2.
Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes & Development. 14 (14): 1810–23. doi:10.1101/gad.14.14.1810 (inactive 2021-01-14). PMC 316791. PMID 10898795.CS1 maint: DOI inactive as of January 2021 (link)
Vasanwala FH, Kusam S, Toney LM, Dent AL (August 2002). "Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene". Journal of Immunology. 169 (4): 1922–9. doi:10.4049/jimmunol.169.4.1922. PMID 12165517.
David G, Alland L, Hong SH, Wong CW, DePinho RA, Dejean A (May 1998). "Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein". Oncogene. 16 (19): 2549–56. doi:10.1038/sj.onc.1202043. PMID 9627120.
Deltour S, Guerardel C, Leprince D (December 1999). "Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: the case of HIC-1 and gammaFBP-B". Proceedings of the National Academy of Sciences of the United States of America. 96 (26): 14831–6. Bibcode:1999PNAS...9614831D. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298.
Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". The Journal of Biological Chemistry. 277 (24): 22045–52. doi:10.1074/jbc.M201736200. PMID 11929873.
Gupta S, Jiang M, Anthony A, Pernis AB (December 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine. 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
Wong CW, Privalsky ML (October 1998). "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". The Journal of Biological Chemistry. 273 (42): 27695–702. doi:10.1074/jbc.273.42.27695. PMID 9765306.
Davies JM, Hawe N, Kabarowski J, Huang QH, Zhu J, Brand NJ, Leprince D, Dhordain P, Cook M, Morriss-Kay G, Zelent A (January 1999). "Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene". Oncogene. 18 (2): 365–75. doi:10.1038/sj.onc.1202332. PMID 9927193.
Oestreich KJ, Huang AC, Weinmann AS (May 2011). "The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns". The Journal of Experimental Medicine. 208 (5): 1001–13. doi:10.1084/jem.20102144. PMC 3092354. PMID 21518797.
Dhordain P, Albagli O, Honore N, Guidez F, Lantoine D, Schmid M, The HD, Zelent A, Koken MH (December 2000). "Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF". Oncogene. 19 (54): 6240–50. doi:10.1038/sj.onc.1203976. PMID 11175338.

External links

BCL6+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Human BCL6 genome location and BCL6 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000113916 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022508 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] "Entrez Gene: BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51)".

[pmid8235596-6] Ye BH, Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R (October 1993). "Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma". Science. 262 (5134): 747–50. Bibcode:1993Sci...262..747Y. doi:10.1126/science.8235596. PMID 8235596.

[pmid8220427-7] Kerckaert JP, Deweindt C, Tilly H, Quief S, Lecocq G, Bastard C (September 1993). "LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas". Nature Genetics. 5 (1): 66–70. doi:10.1038/ng0993-66. PMID 8220427. S2CID 12575122.

[pmid8618933-8] Migliazza A, Martinotti S, Chen W, Fusco C, Ye BH, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R (December 1995). "Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma". Proceedings of the National Academy of Sciences of the United States of America. 92 (26): 12520–4. Bibcode:1995PNAS...9212520M. doi:10.1073/pnas.92.26.12520. PMC 40389. PMID 8618933.

[pmid18675787-9] Shen Y, Ge B, Ramachandrareddy H, McKeithan T, Chan WC (October 2008). "Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor". Biochemical and Biophysical Research Communications. 375 (2): 190–3. doi:10.1016/j.bbrc.2008.07.116. PMC 2573862. PMID 18675787.

[10] Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, Wang YH, Dong C (August 2009). "Bcl6 mediates the development of T follicular helper cells". Science. 325 (5943): 1001–5. Bibcode:2009Sci...325.1001N. doi:10.1126/science.1176676. PMC 2857334. PMID 19628815.

[11] Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent AL, Craft J, Crotty S (August 2009). "Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation". Science. 325 (5943): 1006–10. Bibcode:2009Sci...325.1006J. doi:10.1126/science.1175870. PMC 2766560. PMID 19608860.

[Leong-12] Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2nd ed.). Greenwich Medical Media, Ltd. p. 29. ISBN 978-1-84110-100-2.

[pmid10898795-13] Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes & Development. 14 (14): 1810–23. doi:10.1101/gad.14.14.1810 (inactive 2021-01-14). PMC 316791. PMID 10898795.CS1 maint: DOI inactive as of January 2021 (link)

[pmid12165517-14] Vasanwala FH, Kusam S, Toney LM, Dent AL (August 2002). "Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene". Journal of Immunology. 169 (4): 1922–9. doi:10.4049/jimmunol.169.4.1922. PMID 12165517.

[pmid9627120-15] David G, Alland L, Hong SH, Wong CW, DePinho RA, Dejean A (May 1998). "Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein". Oncogene. 16 (19): 2549–56. doi:10.1038/sj.onc.1202043. PMID 9627120.

[pmid10611298-16] Deltour S, Guerardel C, Leprince D (December 1999). "Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: the case of HIC-1 and gammaFBP-B". Proceedings of the National Academy of Sciences of the United States of America. 96 (26): 14831–6. Bibcode:1999PNAS...9614831D. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298.

[pmid11929873-17] Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". The Journal of Biological Chemistry. 277 (24): 22045–52. doi:10.1074/jbc.M201736200. PMID 11929873.

[pmid10601358-18] Gupta S, Jiang M, Anthony A, Pernis AB (December 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". The Journal of Experimental Medicine. 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.

[pmid9765306-19] Wong CW, Privalsky ML (October 1998). "Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6". The Journal of Biological Chemistry. 273 (42): 27695–702. doi:10.1074/jbc.273.42.27695. PMID 9765306.

[pmid9927193-20] Davies JM, Hawe N, Kabarowski J, Huang QH, Zhu J, Brand NJ, Leprince D, Dhordain P, Cook M, Morriss-Kay G, Zelent A (January 1999). "Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene". Oncogene. 18 (2): 365–75. doi:10.1038/sj.onc.1202332. PMID 9927193.

[pmid21518797-21] Oestreich KJ, Huang AC, Weinmann AS (May 2011). "The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns". The Journal of Experimental Medicine. 208 (5): 1001–13. doi:10.1084/jem.20102144. PMC 3092354. PMID 21518797.

[pmid11175338-22] Dhordain P, Albagli O, Honore N, Guidez F, Lantoine D, Schmid M, The HD, Zelent A, Koken MH (December 2000). "Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF". Oncogene. 19 (54): 6240–50. doi:10.1038/sj.onc.1203976. PMID 11175338.