Specific inhibition of p300-HAT alters global gene expression and represses HIV replication

被引：155

作者：

Mantelingu, K.

Reddy, B. A. Ashok

Swaminathan, V.

Hari Kishore, A.

Siddappa, Nagadenahalli B.

Pavan Kumar, G. V.

Nagashankar, G.

Natesh, Nagashayana

Roy, Siddhartha

Sadhale, Parag P.

Ranga, Udaykumar

Narayana, Chandrablhas

Kundu, Tapas K.

机构：

[1] Jawaharlal Nehru Ctr Adv Sci Res, Transcript & Dis Lab, Mol Biol & Genet Unit, Bangalore, Karnataka, India

[2] Jawaharlal Nehru Ctr Adv Sci Res, Mol Virol Lab, Mol Biol & Genet Unit, Bangalore, Karnataka, India

[3] Jawaharlal Nehru Ctr Adv Sci Res, Light Scattering Lab, Chem & Phys Mat Unit, Bangalore, Karnataka, India

[4] Cent Govt Hlth Scheme Dispensary 3, Bangalore, Karnataka, India

[5] Indian Inst Sci, Mol Biophys Unit, Bangalore, Karnataka, India

[6] Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore, Karnataka, India

来源：

CHEMISTRY & BIOLOGY | 2007年 / 14卷 / 06期

关键词：

D O I：

10.1016/j.chembiol.2007.04.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：645 / 657

页数：13

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