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

Karanam Balasubramanyam, Radhika A. Varier, Mohammed Altaf, Venkatesh Swaminathan, Nagadenahalli B. Siddappa, Udaykumar Ranga, Tapas K. Kundu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)51163-51171
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number49
DOIs
StatePublished - Dec 3 2004

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CREB-Binding Protein
Histone Acetyltransferases
Acetylation
Acetyltransferases
Curcumin
Transcription
Histones
Chromatin
Proteins
Viruses
Human Immunodeficiency Virus tat Gene Products
HIV
Lead compounds
Curcuma
Spices
Viral DNA
Gene Expression Regulation
Human Genome
Giant Cells
Post Translational Protein Processing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. / Balasubramanyam, Karanam; Varier, Radhika A.; Altaf, Mohammed; Swaminathan, Venkatesh; Siddappa, Nagadenahalli B.; Ranga, Udaykumar; Kundu, Tapas K.

In: Journal of Biological Chemistry, Vol. 279, No. 49, 03.12.2004, p. 51163-51171.

Research output: Contribution to journalArticle

Balasubramanyam, Karanam ; Varier, Radhika A. ; Altaf, Mohammed ; Swaminathan, Venkatesh ; Siddappa, Nagadenahalli B. ; Ranga, Udaykumar ; Kundu, Tapas K. / Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 49. pp. 51163-51171.
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