BCL6とは？わかりやすく解説

BCL6
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1R28, 1R29, 1R2B, 2EN2, 2EOS, 2LCE, 2YRM, 3BIM, 3E4U, 3LBZ, 4CP3, 4U2M
識別子
記号	BCL6, BCL5, BCL6A, LAZ3, ZBTB27, ZNF51, B-cell CLL/lymphoma 6, B cell CLL/lymphoma 6, transcription repressor, BCL6 transcription repressor
外部ID	OMIM: 109565 MGI: 107187 HomoloGene: 7640 GeneCards: BCL6
遺伝子の位置 (ヒト)
染色体	3番染色体 (ヒト)
終点	187,745,725 bp
遺伝子の位置 (マウス)
染色体	16番染色体 (マウス)
終点	23,807,602 bp
RNA発現パターン
	; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• sequence-specific DNA binding; • DNA結合; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • DNA-binding transcription factor activity; • intronic transcription regulatory region sequence-specific DNA binding; • クロマチン結合; • 金属イオン結合; • 血漿タンパク結合; • DNA-binding transcription repressor activity, RNA polymerase II-specific; • 核酸結合; • chromatin DNA binding; • identical protein binding; • DNA-binding transcription factor activity, RNA polymerase II-specific;
細胞の構成要素	• replication fork; • 細胞核; • 核質; • ゴルジ体;
生物学的プロセス	• regulation of germinal center formation; • positive regulation of histone deacetylation; • negative regulation of T-helper 2 cell differentiation; • タンパク質局在化; • negative regulation of mast cell cytokine production; • regulation of transcription, DNA-templated; • 免疫系プロセス; • regulation of GTPase activity; • regulation of transcription by RNA polymerase II; • 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 by RNA polymerase II; • transcription, DNA-templated; • type 2 immune response; • DNA損傷刺激に対する細胞応答; • negative regulation of cell-matrix adhesion; • regulation of cell population proliferation; • positive regulation of B cell proliferation; • negative regulation of cell growth; • Rho protein signal transduction; • cell morphogenesis; • 精子発生; • 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; • B cell differentiation; • 炎症反応; • negative regulation of transcription, DNA-templated; • actin cytoskeleton organization; • negative regulation of cell population 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; • サイトカイン媒介シグナル伝達経路;
	出典:Amigo / QuickGO
オルソログ
	604
	12053
	ENSG00000113916
	ENSMUSG00000022508
	P41182,C9JL16
	P41183
	NM_001130845; NM_001134738; NM_001706; NM_138931
	NM_009744; NM_001348026
	NP_001124317; NP_001128210; NP_001697
	NP_001334955; NP_033874
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

BCL6（B-cell/CLL lymphoma 6）は、ヒトではBCL6遺伝子にコードされるタンパク質である^[5]。BCL2、BCL3 、BCL7A（英語版）、BCL9、BCL10と同様、リンパ腫において臨床的に重要である。

機能

BCL6遺伝子にコードされるBCL6タンパク質は進化的に保存されたジンクフィンガー型転写因子であり、N末端にPOZ/BTBドメインを持つ。このタンパク質は配列特異的な転写リプレッサーとして作用し、B細胞のSTAT依存的なIL-4応答を調節することが示されている。このタンパク質はいくつかのコリプレッサー複合体と相互作用して転写を阻害する。BCL6遺伝子はびまん性大細胞型B細胞リンパ腫（DLBCL）において高頻度で転座や高変異が生じていることが知られており^[6]^[7]^[8]、DLBCLの発症に寄与している。エクソン7がスキップされたスプライスバリアントは、DNA結合ドメインの最初の2つのジンクフィンガーを欠く短いタンパク質をコードする^[9]。

生理学的には、BCL6はナイーブヘルパーT細胞の濾胞性ヘルパーT細胞（TFH細胞）への分化をもたらす主要な転写因子である^[10]。その作用は転写因子Blimp-1（英語版）による負の調節を受ける^[11]。

診断における有用性

組織切片中のBCL6の存在は免疫染色によって確認される。BCL6は非腫瘍性胚中心と腫瘍性胚中心のB細胞にのみ存在する。そのため、リンパ節における反応性過形成（英語版）や、バーキットリンパ腫、濾胞性リンパ腫、結節性リンパ球優位型のホジキンリンパ腫など、濾胞性B細胞（英語版）由来のリンパ腫を示す。また、Bcl-2抗原に対する抗体と併用することで、Bcl-2陰性の良性過形成に見られる濾胞と、腫瘍性濾胞を区別することができる^[12]。

相互作用

BCL6は次に挙げる因子と相互作用することが示されている。

出典

1 2 3 GRCh38: Ensembl release 89: ENSG00000113916 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022508 - Ensembl, May 2017
↑ Human PubMed Reference:
↑ Mouse PubMed Reference:
↑ “Entrez Gene: BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51)”. 2021年9月26日閲覧。
↑ “Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma”. Science 262 (5134): 747–50. (October 1993). Bibcode:1993Sci...262..747Y. doi:10.1126/science.8235596. PMID 8235596.
↑ “LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas”. Nature Genetics 5 (1): 66–70. (September 1993). doi:10.1038/ng0993-66. PMID 8220427.
↑ “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. (December 1995). Bibcode:1995PNAS...9212520M. doi:10.1073/pnas.92.26.12520. PMC 40389. PMID 8618933.
↑ “Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor”. Biochemical and Biophysical Research Communications 375 (2): 190–3. (October 2008). doi:10.1016/j.bbrc.2008.07.116. PMC 2573862. PMID 18675787.
↑ “Bcl6 mediates the development of T follicular helper cells”. Science 325 (5943): 1001–5. (August 2009). Bibcode:2009Sci...325.1001N. doi:10.1126/science.1176676. PMC 2857334. PMID 19628815.
↑ “Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation”. Science 325 (5943): 1006–10. (August 2009). 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
1 2 “BCoR, a novel corepressor involved in BCL-6 repression”. Genes & Development 14 (14): 1810–23. (July 2000). doi:10.1101/gad.14.14.1810. PMC 316791. PMID 10898795.
↑ “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. (August 2002). doi:10.4049/jimmunol.169.4.1922. PMID 12165517.
1 2 “Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein”. Oncogene 16 (19): 2549–56. (May 1998). doi:10.1038/sj.onc.1202043. PMID 9627120.
1 2 “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. (December 1999). Bibcode:1999PNAS...9614831D. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298.
1 2 3 “Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor”. The Journal of Biological Chemistry 277 (24): 22045–52. (June 2002). doi:10.1074/jbc.M201736200. PMID 11929873.
↑ “Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4”. The Journal of Experimental Medicine 190 (12): 1837–48. (December 1999). doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.
↑ “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. (October 1998). doi:10.1074/jbc.273.42.27695. PMID 9765306.
↑ “Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene”. Oncogene 18 (2): 365–75. (January 1999). doi:10.1038/sj.onc.1202332. PMID 9927193.
↑ “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. (May 2011). doi:10.1084/jem.20102144. PMC 3092354. PMID 21518797.
↑ “Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF”. Oncogene 19 (54): 6240–50. (December 2000). doi:10.1038/sj.onc.1203976. PMID 11175338.

外部リンク

BCL6 protein, human - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）
Human BCL6 genome location and BCL6 gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000113916 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022508 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[:0-5] “Entrez Gene: BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51)”. 2021年9月26日閲覧。

[pmid8235596-6] “Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma”. Science 262 (5134): 747–50. (October 1993). Bibcode:1993Sci...262..747Y. doi:10.1126/science.8235596. PMID 8235596.

[pmid8220427-7] “LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas”. Nature Genetics 5 (1): 66–70. (September 1993). doi:10.1038/ng0993-66. PMID 8220427.

[pmid8618933-8] “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. (December 1995). Bibcode:1995PNAS...9212520M. doi:10.1073/pnas.92.26.12520. PMC 40389. PMID 8618933.

[pmid18675787-9] “Alternative splicing generates a short BCL6 (BCL6S) isoform encoding a compact repressor”. Biochemical and Biophysical Research Communications 375 (2): 190–3. (October 2008). doi:10.1016/j.bbrc.2008.07.116. PMC 2573862. PMID 18675787.

[:1-10] “Bcl6 mediates the development of T follicular helper cells”. Science 325 (5943): 1001–5. (August 2009). Bibcode:2009Sci...325.1001N. doi:10.1126/science.1176676. PMC 2857334. PMID 19628815.

[:2-11] “Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation”. Science 325 (5943): 1006–10. (August 2009). 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] 1 2 “BCoR, a novel corepressor involved in BCL-6 repression”. Genes & Development 14 (14): 1810–23. (July 2000). doi:10.1101/gad.14.14.1810. PMC 316791. PMID 10898795.

[pmid12165517-14] “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. (August 2002). doi:10.4049/jimmunol.169.4.1922. PMID 12165517.

[pmid9627120-15] 1 2 “Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein”. Oncogene 16 (19): 2549–56. (May 1998). doi:10.1038/sj.onc.1202043. PMID 9627120.

[pmid10611298-16] 1 2 “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. (December 1999). Bibcode:1999PNAS...9614831D. doi:10.1073/pnas.96.26.14831. PMC 24733. PMID 10611298.

[pmid11929873-17] 1 2 3 “Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor”. The Journal of Biological Chemistry 277 (24): 22045–52. (June 2002). doi:10.1074/jbc.M201736200. PMID 11929873.

[pmid10601358-18] “Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4”. The Journal of Experimental Medicine 190 (12): 1837–48. (December 1999). doi:10.1084/jem.190.12.1837. PMC 2195723. PMID 10601358.

[pmid9765306-19] “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. (October 1998). doi:10.1074/jbc.273.42.27695. PMID 9765306.

[pmid9927193-20] “Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene”. Oncogene 18 (2): 365–75. (January 1999). doi:10.1038/sj.onc.1202332. PMID 9927193.

[pmid21518797-21] “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. (May 2011). doi:10.1084/jem.20102144. PMC 3092354. PMID 21518797.

[pmid11175338-22] “Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF”. Oncogene 19 (54): 6240–50. (December 2000). doi:10.1038/sj.onc.1203976. PMID 11175338.

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BCL6とは？わかりやすく解説

BCL6

機能

診断における有用性

相互作用

出典

関連文献

関連項目

外部リンク

英和和英テキスト翻訳

「BCL6」の関連用語

BCL6とは？ わかりやすく解説

BCL6

機能

診断における有用性

相互作用

出典

関連文献

関連項目

外部リンク

英和和英テキスト翻訳

「BCL6」の関連用語

BCL6とは？わかりやすく解説