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Reciprocal negative regulation between the tumor suppressor protein p53 and B cell CLL/lymphoma 6 (BCL6) via control of caspase-1 expression

Authors
 Min-Kyeong Kim  ;  Ji-Yang Song  ;  Dong-In Koh  ;  Jin Young Kim  ;  Masahiko Hatano  ;  Bu-Nam Jeon  ;  Min-Young Kim  ;  Su-Yeon Cho  ;  Kyung-Sup Kim  ;  Man-Wook Hur 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.294(1) : 299-313, 2019 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2019
Keywords
BCL6 ; E1A binding protein p300 (P300) ; acetylation ; cancer development ; caspase 1 (CASP1) ; caspase-1 ; lymphocyte ; lymphoma ; memory B cell ; p300 ; p53 ; post-translational modification (PTM) ; proteolysis
Abstract
Even in the face of physiological DNA damage or expression of the tumor suppressor protein p53, B cell CLL/lymphoma 6 (BCL6) increases proliferation and antagonizes apoptotic responses in B cells. BCL6 represses TP53 transcription and also appears to inactivate p53 at the protein level, and additional findings have suggested negative mutual regulation between BCL6 and p53. Here, using Bcl6 -/- knockout mice, HEK293A and HCT116 p53 -/- cells, and site-directed mutagenesis, we found that BCL6 interacts with p53 and thereby inhibits acetylation of Lys-132 in p53 by E1A-binding protein p300 (p300), a modification that normally occurs upon DNA damage-induced cellular stress and whose abrogation by BCL6 diminished transcriptional activation of p53 target genes, including that encoding caspase-1. Conversely, we also found that BCL6 protein is degraded via p53-induced, caspase-mediated proteolytic cleavage, and the formation of a BCL6-p53-caspase-1 complex. Our results suggest that p53 may block oncogenic transformation by decreasing BCL6 stability via caspase-1 up-regulation, whereas aberrant BCL6 expression inactivates transactivation of p53 target genes, either by inhibiting p53 acetylation by p300 or repressing TP53 gene transcription. These findings have implications for B cell development and lymphomagenesis.
Full Text
http://www.jbc.org/content/294/1/299.long
DOI
10.1074/jbc.RA118.004204
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koh, Dong In(고동인)
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Jeon, Bu Nam(전부남)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167445
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