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P53 promotes BCL6 degradation by caspases and BCL6 modulates p300-mediated p53 acetylation to suppress cell cycle arrest and apoptosis

Other Titles
 P53은 caspases에 의한 BCL6 분해를 촉진하고, BCL6는 p300에 의한 p53의 아세틸화를 조절하여 세포주기 정지와 세포사멸을 억제한다 
 Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) 
Issue Date
Expression of the human POK family transcription factor BCL6, critical for germinal-center formation, is deregulated in 40% of diffuse large B-cell lymphomas (DLBCLs). Previous studies showed that BCL6 regulates the cell cycle and modulates DNA damage-induced apoptotic responses in B-cells, and also binds to the TP53 promoter to represses TP53 transcription. BCL6 also appears to functionally inactivate p53 activity at the protein level via a mechanism that remains unclear. Here, we show that BCL6 interacts with p53 to decrease expression of the p53 target genes CDKN1A and NOXA by modulating acetylation of p53 at lysine 132 by the acetyltransferase p300. This unique BCL6-regulated acetylation of p53 alters its DNA binding and transcriptional activity at p53 target genes, in addition to directly regulating TP53 gene transcription itself. Conversely, p53 can decrease BCL6 expression at the protein level, which involves a complex interaction between p53, BCL6 and various caspases, ultimately resulting in BCL6 proteolytic cleavage by the activated form of caspase-1, -4 and -5. While p53 does not directly increase the transcription of caspase genes, it does play a role in the formation of the BCL6-p53-caspase complex. To substantiate this activity, we show that a BCL6-mediated p53 acetylation mimic and “hot spot” p53 mutant proteins could not decrease BCL6 protein stability. Taken together my data suggests that p53 may block oncogenesis by decreasing BCL6 expression, while overexpressed BCL6 can inactivate p53 activity, either by modulating p53 acetylation by p300 and/or repressing TP53 gene transcription.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 3. Dissertation
Yonsei Authors
Kim, Min Kyeong(김민경)
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