Curcumin, a Novel p300/CREB-binding Protein-specific Inhibitor of Acetyltransferase, Represses the Acetylation of Histone/Nonhistone Proteins and Histone Acetyltransferase-dependent Chromatin…

By K. Balasubramanyam, Radhika A. Varier, M. Altaf, V. Swaminathan, N. Siddappa, U. Ranga, T. Kundu. Journal of Biological Chemistry, 2004

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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, non-toxic curcumin, which targets p300/CBP, may serve as a lead compound in combinatorial HIV therapeutics.

Subfields: Molecular Biology

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Citations in the corpus

Cancer epigenetics reaches mainstream oncology (2011, background): “Curcumin is an EP300- and CREBBP-specific inhibitor capable of repressing EP300-mediated p53 acetylation in vivo”
Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases (2008, methodology): “…et al., 2005), inhibition of HIV-1 integrase (Mazumder et al., 1995), inhibition of p300/CREB-binding protein-specific acetyltransferase, repression of the acetylation of histone/nonhistone proteins, and histone acetyltransferase-dependent chromatin transcription (Balasubramanyam et al., 2004).”
Distinct roles of GCN5/PCAF‐mediated H3K9ac and CBP/p300‐mediated H3K18/27ac in nuclear receptor transactivation (2011, background): “Further, treating wild-type MEFs with curcumin, an inhibitor of CBP/p300 HAT activities (Balasubramanyam et al, 2004), inhibited GW-induced H3K18/K27ac and recruitment of Pol II on Angptl4 promoter, and blocked GW-induced expression of Angptl4 and other PPARd target genes (Figure 6F and G).”
Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor (2010, background): “Several reports of p300/CBP HAT inhibitors identified through screens or based on bisubstrate analogs have been published (Lau et al., 2000b; Thompson et al., 2001; Zheng et al., 2005; Guidez et al., 2005; Liu et al., 2008a; Stimson et al., 2005; Balasubramanyam et al., 2003; Balasubramanyam et al.,”
Targets of curcumin (2011, background): “It was documented that curcumin specifically repressed the P300/ CBP activity, resulting in several effects, including attenuation of inflammatory responses in human tracheal smooth muscle cells [237], inhibition of human immunodeficiency virus proliferation [238], and suppression of the proliferati”