國家衛生研究院 NHRI:Item 3990099045/5911

NHRI > Institute of Biotechnology and Pharmaceutical Research > Hsing-Pang Hsieh > Periodical Articles > Item 3990099045/5911

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5911

Title:	Inhibition of HIV-1 Tat-mediated transcription by a coumarin derivative, BPRHIV001, through the Akt pathway
Authors:	Lin, PH;Ke, YY;Su, CT;Shiao, HY;Hsieh, HP;Chao, YK;Lee, CN;Kao, CL;Chao, YS;Chang, SY
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	The human immunodeficiency virus type 1 (HIV-1)-encoded RNA-binding protein Tat is known to play an essential role in viral gene expression. In the search for novel compounds to inhibit Tat transactivity, one coumarin derivative, BPRHIV001, was identified, with a 50% effective concentration (EC(50)) against HIV-1 at 1.3 nM. BPRHIV001 is likely to exert its effects at the stage after initiation of RNAPII elongation since Tat protein expression and the assembly of the Tat/P-TEFb complex remained unchanged. Next, a reduction of the p300 protein level, known to modulate Tat function through acetylation, was observed upon BPRHIV001 treatment, while the p300 mRNA level was unaffected. A concordant reduction of phosphorylated Akt, which was shown to be closely related to p300 stability, was observed in the presence of BPRHIV001 and was accompanied by a decrease of phosphorylated PDPK1, a well-known Akt activator. Furthermore, the docking analysis revealed that the reduced PDPK1 phosphorylation likely resulted from the allosteric effect of interaction between BPRHIV001 and PDPK1. With strong synergistic effects with current reverse transcriptase inhibitors, BPRHIV001 has the potential to become a promising lead compound for the development of a novel therapeutic agent against HIV-1 infection.
Date:	2011-09
Relation:	Journal of Virology. 2011 Sep;85(17):9114-9126
Link to:	http://dx.doi.org/10.1128/jvi.00175-11
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-538X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000293626100060
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80052286458
Appears in Collections:	[Hsing-Pang Hsieh] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles

Files in This Item:

File	Description	Size	Format
ISI000293626100060.pdf		3340Kb	Adobe PDF	702	View/Open

Loading...