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Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation.

Authors
 Kyung-Chul Choi  ;  Myung Gu Jung  ;  Yoo-Hyun Lee  ;  Joo Chun Yoon  ;  Seung Hyun Kwon  ;  Hee-Bum Kang  ;  Mi-Jeong Kim  ;  Jeong-Heon Cha  ;  Young Jun Kim  ;  Woo Jin Jun  ;  Jae Myun Lee  ;  Ho-Geun Yoon 
Citation
 Cancer Research, Vol.69(2) : 583-592, 2009 
Journal Title
 Cancer Research 
ISSN
 0008-5472 
Issue Date
2009
Abstract
Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-kappaB (NF-kappaB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 micromol/L, EGCG abrogates p300-induced p65 acetylation in vitro and in vivo, increases the level of cytosolic IkappaBalpha, and suppresses tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. We also showed that EGCG prevents TNFalpha-induced p65 translocation to the nucleus, confirming that hyperacetylation is critical for NF-kappaB translocation as well as activity. Furthermore, EGCG treatment inhibited the acetylation of p65 and the expression of NF-kappaB target genes in response to diverse stimuli. Finally, EGCG reduced the binding of p300 to the promoter region of interleukin-6 gene with an increased recruitment of HDAC3, which highlights the importance of the balance between HATs and histone deacetylases in the NF-kappaB-mediated inflammatory signaling pathway. Importantly, EGCG at 50 micromol/L dose completely blocks EBV infection-induced cytokine expression and subsequently the EBV-induced B lymphocyte transformation. These results show the crucial role of acetylation in the development of inflammatory-related diseases
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DOI
10.1158/0008-5472.CAN-08-2442
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
강희범(Kang, Hee Bum)
권승현(Kwon, Seung Hyun)
윤주천(Yoon, Joo Chun)
윤호근(Yoon, Ho Geun) ORCID logo https://orcid.org/0000-0003-2718-3372
이재면(Lee, Jae Myun) ORCID logo https://orcid.org/0000-0002-5273-3113
차정헌(Cha, Jung Heon) ORCID logo https://orcid.org/0000-0002-9385-2653
최경철(Choi, Kyung Chul)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103634
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