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Acetylation inactivates the transcriptional repressor BCL6
Oksana R Bereshchenko1, Wei Gu, Riccardo Dalla-Favera
1Institute for Cancer Genetics and the Department of Pathology, Columbia University, New York, New York 10032, USA.
Nature Genetics
|October 29, 2002
Summary
The proto-oncogene BCL6, crucial for germinal-center formation, is inhibited by p300 acetylation. Inhibiting acetylation pathways halts B-cell lymphoma cell growth, offering therapeutic potential.
Area of Science:
- Molecular Biology
- Cancer Biology
- Epigenetics
Background:
- The proto-oncogene BCL6 is a transcriptional repressor vital for germinal-center formation.
- BCL6 dysregulation is implicated in B-cell lymphoma pathogenesis.
Purpose of the Study:
- To investigate the regulatory mechanisms of BCL6.
- To explore the role of p300 and acetylation in BCL6 function.
- To assess therapeutic strategies targeting BCL6 acetylation in B-cell lymphomas.
Main Methods:
- In vivo binding and acetylation assays using p300 and BCL6.
- Assessment of BCL6's transcriptional repressor activity.
- Analysis of BCL6 acetylation in normal and cancerous B cells.
- Pharmacological inhibition of HDAC and SIR2 pathways.
Main Results:
- p300 binds and acetylates BCL6, inhibiting its transcriptional repressor function.
- Acetylation disrupts BCL6's recruitment of histone deacetylases (HDACs).
- Pharmacological inhibition of HDAC- and SIR2-dependent pathways induces BCL6 acetylation, leading to cell-cycle arrest and apoptosis in lymphoma cells.
Conclusions:
- Acetylation by p300 is a novel mechanism for BCL6 regulation.
- Targeting BCL6 acetylation pathways presents a potential therapeutic strategy for B-cell lymphomas.
- Acetylation can inhibit transcriptional repressors, expanding the understanding of transcriptional regulation.