BCL6

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B-cell CLL/lymphoma 6
Protein BCL6 PDB 1r28.png
PDB rendering based on 1r28.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols BCL6 ; BCL5; BCL6A; LAZ3; ZBTB27; ZNF51
External IDs OMIM109565 MGI107187 HomoloGene7640 GeneCards: BCL6 Gene
RNA expression pattern
PBB GE BCL6 203140 at tn.png
PBB GE BCL6 215990 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 604 12053
Ensembl ENSG00000113916 ENSMUSG00000022508
UniProt P41182 P41183
RefSeq (mRNA) NM_001130845 NM_009744
RefSeq (protein) NP_001124317 NP_033874
Location (UCSC) Chr 3:
187.44 – 187.46 Mb
Chr 16:
23.97 – 23.99 Mb
PubMed search [1] [2]

B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.[1] 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),[2][3][4] 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.[5]

Physiologically, BCL6 is a master transcription factor which leads the differentiation of naive helper T cells in Follicular Helper T cells (TFH cells).[6] Its action is negatively regulated by the gene PRDM1 encoding the transcription factor Blimp-1.[7]

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.[8]

Interactions[edit]

BCL6 has been shown to interact with

References[edit]

  1. ^ "Entrez Gene: BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51)". 
  2. ^ 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. 
  3. ^ 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". Nat. Genet. 5 (1): 66–70. doi:10.1038/ng0993-66. PMID 8220427. 
  4. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12520–4. doi:10.1073/pnas.92.26.12520. PMC 40389. PMID 8618933. 
  5. ^ Shen Y, Ge B, Ramachandrareddy H, McKeithan T, Chan WC (October 2008). "Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor". Biochem. Biophys. Res. Commun. 375 (2): 190–3. doi:10.1016/j.bbrc.2008.07.116. PMC 2573862. PMID 18675787. 
  6. ^ Roza I. Nurieva, Yeonseok Chung, Gustavo J. Martinez, Xuexian O. Yang, Shinya Tanaka, Tatyana D. Matskevitch, Yi-Hong Wang, Chen Dong (August 2009). "Bcl6 Mediates the Development of T Follicular Helper Cells". Science 325 (5943): 1001–1005. doi:10.1126/science.1176676. PMID 19628815. 
  7. ^ Robert J. Johnston, Amanda C. Poholek, Daniel DiToro, Isharat Yusuf, Danelle Eto, Burton Barnett, Alexander L. Dent, Joe Craft, Shane Crotty (August 2009). "Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation". Science 325 (5943): 1006–1010. doi:10.1126/science.1175870. PMID 19608860. 
  8. ^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. p. 29. ISBN 1-84110-100-1. 
  9. ^ a b Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes Dev. 14 (14): 1810–23. doi:10.1101/gad.14.14.1810. PMC 316791. PMID 10898795. 
  10. ^ 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". J. Immunol. 169 (4): 1922–9. doi:10.4049/jimmunol.169.4.1922. PMID 12165517. 
  11. ^ 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. 
  12. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 96 (26): 14831–6. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298. 
  13. ^ 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". J. Biol. Chem. 277 (24): 22045–52. doi:10.1074/jbc.M201736200. PMID 11929873. 
  14. ^ Gupta S, Jiang M, Anthony A, Pernis AB (December 1999). "Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4". J. Exp. Med. 190 (12): 1837–48. doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358. 
  15. ^ 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". J. Biol. Chem. 273 (42): 27695–702. doi:10.1074/jbc.273.42.27695. PMID 9765306. 
  16. ^ 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. 
  17. ^ Oestreich KJ, Huang AC, Weinmann AS (May 2011). "The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns". J. Exp. Med. 208 (5): 1001–13. doi:10.1084/jem.20102144. PMC 3092354. PMID 21518797. 
  18. ^ 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 (2003). "Non-immunoglobulin/BCL6 gene fusion in diffuse large B-cell lymphoma: prognostic implications". Leuk. Lymphoma 43 (7): 1375–81. doi:10.1080/10428190290033305. PMID 12389616. 
  • Niu H (2003). "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 (2003). "[A role for Bcl6 in immune memory development]". Tanpakushitsu Kakusan Koso 47 (16 Suppl): 2306–12. PMID 12518453. 
  • Ohno H (2004). "Pathogenetic role of BCL6 translocation in B-cell non-Hodgkin's lymphoma". Histol. Histopathol. 19 (2): 637–50. PMID 15024721. 
  • Pasqualucci L, Bereschenko O, Niu H et al. (2004). "Molecular pathogenesis of non-Hodgkin's lymphoma: the role of Bcl-6". Leuk. Lymphoma. 44 Suppl 3: S5–12. doi:10.1080/10428190310001621588. PMID 15202519. 
  • Jardin F, Ruminy P, Bastard C, Tilly H (2007). "The BCL6 proto-oncogene: a leading role during germinal center development and lymphomagenesis". Pathol. Biol. 55 (1): 73–83. doi:10.1016/j.patbio.2006.04.001. PMID 16815642. 

See also[edit]

External links[edit]

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