BCL6

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BCL6
Protein BCL6 PDB 1r28.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBCL6, BCL5, BCL6A, LAZ3, ZBTB27, ZNF51, B-cell CLL/lymphoma 6, B cell CLL/lymphoma 6
External IDsMGI: 107187 HomoloGene: 7640 GeneCards: BCL6
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for BCL6
Genomic location for BCL6
Band3q27.3Start187,721,377 bp[1]
End187,745,727 bp[1]
RNA expression pattern
PBB GE BCL6 215990 s at fs.png

PBB GE BCL6 203140 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001130845
NM_001134738
NM_001706
NM_138931

NM_009744
NM_001348026

RefSeq (protein)

NP_001124317
NP_001128210
NP_001697

NP_001334955
NP_033874

Location (UCSC)Chr 3: 187.72 – 187.75 MbChr 16: 23.97 – 23.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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[edit]

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[edit]

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[edit]

BCL6 has been shown to interact with

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000113916 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022508 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ "Entrez Gene: BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51)".
  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. doi:10.1126/science.8235596. PMID 8235596.
  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.
  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. doi:10.1073/pnas.92.26.12520. PMC 40389. PMID 8618933.
  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. 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. doi:10.1126/science.1175870. PMC 2766560. PMID 19608860.
  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 1-84110-100-1.
  13. ^ a b 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. PMC 316791. PMID 10898795.
  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.
  15. ^ a b 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.
  16. ^ a b 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. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298.
  17. ^ a b c 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.
  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.
  19. ^ a b 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.
  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.
  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.
  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.

Further reading[edit]

  • Ueda C, Akasaka T, Ohno H (July 2002). "Non-immunoglobulin/BCL6 gene fusion in diffuse large B-cell lymphoma: prognostic implications". Leukemia & Lymphoma. 43 (7): 1375–81. doi:10.1080/10428190290033305. PMID 12389616.
  • Niu H (December 2002). "The proto-oncogene BCL-6 in normal and malignant B cell development". Hematological Oncology. 20 (4): 155–66. doi:10.1002/hon.689. PMID 12469325.
  • Tokuhisa T (December 2002). "[A role for Bcl6 in immune memory development]". Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme. 47 (16 Suppl): 2306–12. PMID 12518453.
  • Ohno H (April 2004). "Pathogenetic role of BCL6 translocation in B-cell non-Hodgkin's lymphoma". Histology and Histopathology. 19 (2): 637–50. PMID 15024721.
  • Pasqualucci L, Bereshchenko O, Bereschenko O, Niu H, Klein U, Basso K, Guglielmino R, Cattoretti G, Dalla-Favera R (2004). "Molecular pathogenesis of non-Hodgkin's lymphoma: the role of Bcl-6". Leukemia & Lymphoma. 44 Suppl 3: S5–12. doi:10.1080/10428190310001621588. PMID 15202519.
  • Jardin F, Ruminy P, Bastard C, Tilly H (February 2007). "The BCL6 proto-oncogene: a leading role during germinal center development and lymphomagenesis". Pathologie-Biologie. 55 (1): 73–83. doi:10.1016/j.patbio.2006.04.001. PMID 16815642.

External links[edit]

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