Mantelingu, K and Reddy, Ashok BA and Swaminathan, V and Kishore, Hari A and Siddappa, Nagadenahalli B and Kumar, Pavan GV and Nagashankar, G and Natesh, Nagashayana and Roy, Siddhartha and Sadhale, Parag P and Ranga, Udaykumar and Narayana, Chandrabhas and Kundu, Tapas K (2007) Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication. In: Chemistry & Biology, 14 (6). pp. 645-657.
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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.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to Elsevier.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit
Division of Biological Sciences > Microbiology & Cell Biology
|Date Deposited:||04 Oct 2007|
|Last Modified:||19 Sep 2010 04:39|
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