Acetylation inactivates the transcriptional repressor BCL6
- PMID: 12402037
- DOI: 10.1038/ng1018
Acetylation inactivates the transcriptional repressor BCL6
Abstract
The proto-oncogene BCL6 encodes a BTB/POZ-zinc finger transcriptional repressor that is necessary for germinal-center formation and has been implicated in the pathogenesis of B-cell lymphomas. Here we show that the co-activator p300 binds and acetylates BCL6 in vivo and inhibits its function. Acetylation disrupts the ability of BCL6 to recruit histone deacetylases (HDACs), thereby hindering its capacity to repress transcription and to induce cell transformation. BCL6 is acetylated under physiologic conditions in normal germinal-center B cells and in germinal center-derived B-cell tumors. Treatment with specific inhibitors shows that levels of acetylation of BCL6 are controlled by both HDAC-dependent and SIR2-dependent pathways. Pharmacological inhibition of these pathways leads to the accumulation of the inactive acetylated BCL6 and to cell-cycle arrest and apoptosis in B-cell lymphoma cells. These results identify a new mechanism of regulation of the proto-oncogene BCL6 with potential for therapeutic exploitation. Furthermore, these findings provide a new mechanism by which acetylation can promote transcription not only by modifying histones and activating transcriptional activators, but also by inhibiting transcriptional repressors.
Similar articles
-
The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.Nature. 2004 Dec 2;432(7017):635-9. doi: 10.1038/nature03147. Nature. 2004. PMID: 15577913
-
BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells.Nat Immunol. 2005 Oct;6(10):1054-60. doi: 10.1038/ni1245. Epub 2005 Sep 4. Nat Immunol. 2005. PMID: 16142238
-
The LAZ3/BCL6 oncogene encodes a sequence-specific transcriptional inhibitor: a novel function for the BTB/POZ domain as an autonomous repressing domain.Cell Growth Differ. 1995 Dec;6(12):1495-503. Cell Growth Differ. 1995. PMID: 9019154
-
Targeted somatic mutation of the BCL6 proto-oncogene and its impact on lymphomagenesis.Hematology. 2005 Apr;10(2):115-29. doi: 10.1080/10245330400026105. Hematology. 2005. PMID: 16019457 Review.
-
The proto-oncogene BCL-6 in normal and malignant B cell development.Hematol Oncol. 2002 Dec;20(4):155-66. doi: 10.1002/hon.689. Hematol Oncol. 2002. PMID: 12469325 Review.
Cited by
-
Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine.Epigenetics. 2015;10(5):431-45. doi: 10.1080/15592294.2015.1039216. Epigenetics. 2015. PMID: 25923331 Free PMC article.
-
Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata.Hum Mol Genet. 2013 Sep 1;22(17):3568-82. doi: 10.1093/hmg/ddt211. Epub 2013 May 12. Hum Mol Genet. 2013. PMID: 23669349 Free PMC article.
-
BCL-6 suppresses miR-142-3p/5p expression in SLE CD4+ T cells by modulating histone methylation and acetylation of the miR-142 promoter.Cell Mol Immunol. 2020 May;17(5):474-482. doi: 10.1038/s41423-019-0268-3. Epub 2019 Aug 20. Cell Mol Immunol. 2020. PMID: 31431691 Free PMC article.
-
PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival.Blood. 2018 Nov 8;132(19):2026-2039. doi: 10.1182/blood-2018-02-831438. Epub 2018 Aug 6. Blood. 2018. PMID: 30082494 Free PMC article.
-
The transcriptional modulator BCL6 as a molecular target for breast cancer therapy.Oncogene. 2015 Feb 26;34(9):1073-82. doi: 10.1038/onc.2014.61. Epub 2014 Mar 24. Oncogene. 2015. PMID: 24662818 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous
