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

143 Citations (Scopus)

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

Fingerprint

Histone Acetyltransferases
Gene expression
Acetylation
HIV
Gene Expression
Histones
Genes
T-cells
Poisons
Cardiomegaly
Medical problems
Acquired Immunodeficiency Syndrome
Homeostasis
Down-Regulation
Asthma
T-Lymphocytes
Molecules
p300-CBP-associated factor
Neoplasms
Proteins

Keywords

  • CHEMBIOL
  • DNA

ASJC Scopus subject areas

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

Cite this

Mantelingu, K., Reddy, B. A. A., Swaminathan, V., Kishore, A. H., Siddappa, N. B., Kumar, G. V. P., ... 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

Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication. / Mantelingu, K.; Reddy, B. A.Ashok; Swaminathan, V.; Kishore, A. Hari; Siddappa, Nagadenahalli B.; Kumar, G. V.Pavan; Nagashankar, G.; Natesh, Nagashayana; Roy, Siddhartha; Sadhale, Parag P.; Ranga, Udaykumar; Narayana, Chandrabhas; Kundu, Tapas K.

In: Chemistry and Biology, Vol. 14, No. 6, 25.06.2007, p. 645-657.

Research output: Contribution to journalArticle

Mantelingu, K, Reddy, BAA, Swaminathan, V, Kishore, AH, Siddappa, NB, Kumar, GVP, Nagashankar, G, Natesh, N, Roy, S, Sadhale, PP, Ranga, U, Narayana, C & Kundu, TK 2007, 'Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication', Chemistry and Biology, vol. 14, no. 6, pp. 645-657. https://doi.org/10.1016/j.chembiol.2007.04.011
Mantelingu, K. ; Reddy, B. A.Ashok ; Swaminathan, V. ; Kishore, A. Hari ; Siddappa, Nagadenahalli B. ; Kumar, G. V.Pavan ; Nagashankar, G. ; Natesh, Nagashayana ; Roy, Siddhartha ; Sadhale, Parag P. ; Ranga, Udaykumar ; Narayana, Chandrabhas ; Kundu, Tapas K. / Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication. In: Chemistry and Biology. 2007 ; Vol. 14, No. 6. pp. 645-657.
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