Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription

被引:637
作者
Balasubramanyam, K
Varier, RA
Altaf, M
Swaminathan, V
Siddappa, NB
Ranga, U
Kundu, TK [1 ]
机构
[1] Jawaharlal Nehru Ctr Adv Sci Res, Transcript & Dis Lab, Bangalore 560064, Karnataka, India
[2] Jawaharlal Nehru Ctr Adv Sci Res, Mol Virol Lab, Mol Biol & Genet Unit, Bangalore 560064, Karnataka, India
关键词
D O I
10.1074/jbc.M409024200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acetylation of histones and non-histone proteins is an important post-translational modification involved in the regulation of gene expression in eukaryotes and all viral DNA that integrates into the human genome ( e. g. the human immunodeficiency virus). Dysfunction of histone acetyltransferases (HATs) is often associated with the manifestation of several diseases. In this respect, HATs are the new potential targets for the design of therapeutics. In this study, we report that curcumin (diferuloylmethane), a major curcumanoid in the spice turmeric, is a specific inhibitor of the p300/CREB-binding protein (CBP) HAT activity but not of p300/CBP-associated factor, in vitro and in vivo. Furthermore, curcumin could also inhibit the p300-mediated acetylation of p53 in vivo. It specifically represses the p300/CBP HAT activity-dependent transcriptional activation from chromatin but not a DNA template. It is significant that curcumin could inhibit the acetylation of HIV-Tat protein in vitro by p300 as well as proliferation of the virus, as revealed by the repression in syncytia formation upon curcumin treatment in SupT1 cells. Thus, nontoxic curcumin, which targets p300/CBP, may serve as a lead compound in combinatorial HIV therapeutics.
引用
收藏
页码:51163 / 51171
页数:9
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