Functional modification of the transcription factor BCL6 by acetylation

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BCL6, a transcriptional repressor containing zinc-finger domain, is preferentially expressed in germinal-center B-cells. BCL6 controls B-cell development through regulating expression of down-stream target genes including Blimp-1, p27 and MIP-1. Chromosomal translocation involving BCL6 gene is frequently detected in human B-cell lymphomas, suggesting alteration of BCL6 expression is crucial event in lymphomagenesis. To clarify the function of BCL6, we investigated the significance of acetylation, one of post-translational modifications of proteins. We found that BCL6 interacts with histone acetyl-transferase p300 through mid-portion of BCL6, and acetylated by p300. Transcriptional repression activity of BCL6 was remarkably reduced by acetylation. BCL6 also interacted with P/CAF histone acetyl-transferase.We also examined the effects of BCL6 expression on cell proliferation and apoptosis. BCL6 overexpression significantly inhibited apoptosis of lymphoma cells Daudi and, Raji, in response to etoposide and other chemotherapeutic reagents. BCL6 overexpression also inhibited. the increase in reactive oxygen species (ROS) levels and the reduction of mitochondria transmembrane potential (Δψm) in response to etoposide. The ROS scavenger N-acetyl-l-cysteine (NAC) also inhibited the reduction of Δψm and apoptosis as well as the increase in ROS levels in etoposide-treated. lymphoma cells. These observations indicate that BCL6 overexpression inhibits apoptosis of lymphoma cens treated with chemotherapeutic reagents, most likely through enhancement of the antioxidant defense system.