B cell CLL/lymphoma 6 | BTB (POZ) domain containing TFs | IUPHAR/BPS Guide to PHARMACOLOGY

B cell CLL/lymphoma 6

Target id: 2957

Nomenclature: B cell CLL/lymphoma 6

Family: BTB (POZ) domain containing TFs

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     B cell CLL/lymphoma 6 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 706 3q27.3 BCL6 B cell CLL/lymphoma 6
Mouse - 707 16 B1; 16 15.26 cM Bcl6 B cell leukemia/lymphoma 6
Rat - 707 11q23 Bcl6 B-cell CLL/lymphoma 6
Gene and Protein Information Comments
Alternatively spliced transcript variants encoding different protein isoforms have been found for the human gene.
Previous and Unofficial Names
B-cell CLL/lymphoma 6 | LAZ3 | ZBTB27 | zinc finger protein 51 | ZNF51
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
FX1 Hs Binding 5.2 pKd 2
pKd 5.2 (Kd 7x10-6 M) [2]
Description: Binding of compound to BCL6 BTB domain using microscale thermophoresis.
compound 8c [PMID: 28760529] Hs Binding 6.1 – 7.0 pIC50 6
pIC50 7.0 (IC50 1x10-7 M) [6]
Description: In a cell-free ELISA system measuring ability to inhibit BCL6 BTB domain-NCoR interaction.
pIC50 6.1 (IC50 7.2x10-7 M) [6]
Description: In a cell-based mammalian two-hybrid system assessing inhibition of protein-protein interaction between BCL6 BTB domain and BCoR.
Inhibitor Comments
The BCL6 inhibitor 79-6 (PubChem CID 5721353) is commercially available but it is less potent (Kd 138 μM) than the compounds listed in the table above. 79-6 is active in vitro and in vivo, and is reported to be selective for BCL6 over the related transcription factors Kaiso (ZBTB33), HIC1, and PLZF (ZBTB16) [3].
Immunopharmacology Comments
BCL6/corepressor complexes are important for the formation of germinal centers and differentiation and proliferation of lymphocytes. Oncogenic mutations in BCL6 lead to the development of diffuse large B-cell lymphoma cells from germinal center B cells. Disruption of BCL6/corepressor complex formation by pharmacological inhibitors has therefore been identified as a novel drug mechanism with potential for the treatment of autoimmune diseases and cancer [2-3].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 5 GO processes, IEA only
GO:0050727 regulation of inflammatory response IBA
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
GO:0043380 regulation of memory T cell differentiation IEA
GO:0045629 negative regulation of T-helper 2 cell differentiation IEA
GO:0048294 negative regulation of isotype switching to IgE isotypes IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 6 GO processes, IEA only
GO:0045591 positive regulation of regulatory T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0030183 B cell differentiation IEA
GO:0043380 regulation of memory T cell differentiation IEA
GO:0045629 negative regulation of T-helper 2 cell differentiation IEA
GO:0048294 negative regulation of isotype switching to IgE isotypes IEA
GO:0048821 erythrocyte development IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0032764 negative regulation of mast cell cytokine production IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes, IEA only
GO:0045591 positive regulation of regulatory T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0030183 B cell differentiation IEA
GO:0030890 positive regulation of B cell proliferation IEA
GO:0043380 regulation of memory T cell differentiation IEA
GO:0045629 negative regulation of T-helper 2 cell differentiation IEA
GO:0048294 negative regulation of isotype switching to IgE isotypes IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 6 GO processes, IEA only
GO:0002634 regulation of germinal center formation NAS
GO:0045591 positive regulation of regulatory T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0002467 germinal center formation IEA
GO:0043380 regulation of memory T cell differentiation IEA
GO:0045629 negative regulation of T-helper 2 cell differentiation IEA
GO:0048294 negative regulation of isotype switching to IgE isotypes IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 6 GO processes, IEA only
GO:0002634 regulation of germinal center formation NAS
GO:0002903 negative regulation of B cell apoptotic process NAS
click arrow to show/hide IEA associations
GO:0002467 germinal center formation IEA
GO:0030183 B cell differentiation IEA
GO:0030890 positive regulation of B cell proliferation IEA
GO:0048294 negative regulation of isotype switching to IgE isotypes IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 10 GO processes, IEA only
GO:0002634 regulation of germinal center formation NAS
GO:0045591 positive regulation of regulatory T cell differentiation IMP
GO:0050727 regulation of inflammatory response IBA
GO:0050776 regulation of immune response NAS
click arrow to show/hide IEA associations
GO:0030890 positive regulation of B cell proliferation IEA
GO:0032764 negative regulation of mast cell cytokine production IEA
GO:0043380 regulation of memory T cell differentiation IEA
GO:0045629 negative regulation of T-helper 2 cell differentiation IEA
GO:0048294 negative regulation of isotype switching to IgE isotypes IEA
GO:0048821 erythrocyte development IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes, IEA only
GO:0045591 positive regulation of regulatory T cell differentiation IMP
click arrow to show/hide IEA associations
GO:0043380 regulation of memory T cell differentiation IEA
GO:0045629 negative regulation of T-helper 2 cell differentiation IEA
General Comments
B-cell lymphoma 6 (BCL6) protein is a transcriptional repressor that is involved in protein-protein interactions with corepressors such as CL6 corepressor (BCoR) [4], silencing mediator for retinoid and thyroid receptors (SMRT) [1], and nuclear receptor corepressor (NCoR) [5]. Most diffuse large cell lymphomas and many follicular lymphomas contain oncogenic and deregulating mutations in BCL6.

References

Show »

1. Ahmad KF, Melnick A, Lax S, Bouchard D, Liu J, Kiang CL, Mayer S, Takahashi S, Licht JD, Privé GG. (2003) Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain. Mol. Cell, 12 (6): 1551-64. [PMID:14690607]

2. Cardenas MG, Yu W, Beguelin W, Teater MR, Geng H, Goldstein RL, Oswald E, Hatzi K, Yang SN, Cohen J et al.. (2016) Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma. J. Clin. Invest., 126 (9): 3351-62. [PMID:27482887]

3. Cerchietti LC, Ghetu AF, Zhu X, Da Silva GF, Zhong S, Matthews M, Bunting KL, Polo JM, Farès C, Arrowsmith CH et al.. (2010) A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell, 17 (4): 400-11. [PMID:20385364]

4. Ghetu AF, Corcoran CM, Cerchietti L, Bardwell VJ, Melnick A, Privé GG. (2008) Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol. Cell, 29 (3): 384-91. [PMID:18280243]

5. Huynh KD, Bardwell VJ. (1998) The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT. Oncogene, 17 (19): 2473-84. [PMID:9824158]

6. Yasui T, Yamamoto T, Sakai N, Asano K, Takai T, Yoshitomi Y, Davis M, Takagi T, Sakamoto K, Sogabe S et al.. (2017) Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor by utilizing structure-based drug design. Bioorg. Med. Chem., 25 (17): 4876-4886. [PMID:28760529]

How to cite this page

BTB (POZ) domain containing TFs: B cell CLL/lymphoma 6. Last modified on 27/02/2018. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2957.