Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication

K. Mantelingu, B. A.Ashok Reddy, V. Swaminathan, A. Hari Kishore, Nagadenahalli B. Siddappa, G. V.Pavan Kumar, G. Nagashankar, Nagashayana Natesh, Siddhartha Roy, Parag P. Sadhale, Udaykumar Ranga, Chandrabhas Narayana, Tapas K. Kundu

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Reversible acetylation of histone and nonhistone proteins plays pivotal role in cellular homeostasis. Dysfunction of histone acetyltransferases (HATs) leads to several diseases including cancer, neurodegenaration, asthma, diabetes, AIDS, and cardiac hypertrophy. We describe the synthesis and characterization of a set of p300-HAT-specific small-molecule inhibitors from a natural nonspecific HAT inhibitor, garcinol, which is highly toxic to cells. We show that the specific inhibitor selectively represses the p300-mediated acetylation of p53 in vivo. Furthermore, inhibition of p300-HAT down regulates several genes but significantly a few important genes are also upregulated. Remarkably, these inhibitors were found to be nontoxic to T cells, inhibit histone acetylation of HIV infected cells, and consequently inhibit the multiplication of HIV.

Original languageEnglish (US)
Pages (from-to)645-657
Number of pages13
JournalChemistry and Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 25 2007

Keywords

  • CHEMBIOL
  • DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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  • Cite this

    Mantelingu, K., Reddy, B. A. A., Swaminathan, V., Kishore, A. H., Siddappa, N. B., Kumar, G. V. P., Nagashankar, G., Natesh, N., Roy, S., Sadhale, P. P., Ranga, U., Narayana, C., & Kundu, T. K. (2007). Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication. Chemistry and Biology, 14(6), 645-657. https://doi.org/10.1016/j.chembiol.2007.04.011