TY - JOUR
T1 - Specific Inhibition of p300-HAT Alters Global Gene Expression and Represses HIV Replication
AU - Mantelingu, K.
AU - Reddy, B. A.Ashok
AU - Swaminathan, V.
AU - Kishore, A. Hari
AU - Siddappa, Nagadenahalli B.
AU - Kumar, G. V.Pavan
AU - Nagashankar, G.
AU - Natesh, Nagashayana
AU - Roy, Siddhartha
AU - Sadhale, Parag P.
AU - Ranga, Udaykumar
AU - Narayana, Chandrabhas
AU - Kundu, Tapas K.
N1 - Funding Information:
This work was supported by grants from Intramural Research Program of Basic and Clinical Medical Sciences, Xuanwu Hospital, Capital Medical University (Dr Qi, XWYY201709), Educational and Teaching Reform Project of Capital Medical University Xuanwu Hospital (Dr Qi, 2018XWJXGG-24), Beijing Municipal Human Resources and Social Security Bureau (Dr Qi, 2013ZZ121939), National Natural Science Foundation of China (Dr Zhang, 81603572) and Zhejiang Provincial Natural Science Foundation (Dr Zhang, LQ15H270002). The sponsors had no role in the design or conduct of this research.
PY - 2007/6/25
Y1 - 2007/6/25
N2 - 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.
AB - 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.
KW - CHEMBIOL
KW - DNA
UR - http://www.scopus.com/inward/record.url?scp=34250308083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250308083&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2007.04.011
DO - 10.1016/j.chembiol.2007.04.011
M3 - Article
C2 - 17584612
AN - SCOPUS:34250308083
SN - 1074-5521
VL - 14
SP - 645
EP - 657
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 6
ER -