Journal article
Drug 9AA reactivates p21/Waf1 and Inhibits HIV-1 progeny formation
Virology journal, v 5(1), pp 41-41
18 Mar 2008
PMID: 18348731
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
It has been demonstrated that the p53 pathway plays an important role in HIV-1 infection. Previous work from our lab has established a model demonstrating how p53 could become inactivated in HIV-1 infected cells through binding to Tat. Subsequently, p53 was inactivated and lost its ability to transactivate its downstream target gene p21/waf1. P21/waf1 is a well-known cdk inhibitor (CKI) that can lead to cell cycle arrest upon DNA damage. Most recently, the p21/waf1 function was further investigated as a molecular barrier for HIV-1 infection of stem cells. Therefore, we reason that the restoration of the p53 and p21/waf1 pathways could be a possible theraputical arsenal for combating HIV-1 infection. In this current study, we show that a small chemical molecule, 9-aminoacridine (9AA) at low concentrations, could efficiently reactivate p53 pathway and thereby restoring the p21/waf1 function. Further, we show that the 9AA could significantly inhibit virus replication in activated PBMCs, likely through a mechanism of inhibiting the viral replication machinery. A mechanism study reveals that the phosphorylated p53ser15 may be dissociated from binding to HIV-1 Tat protein, thereby activating the p21/waf1 gene. Finally, we also show that the 9AA-activated p21/waf1 is recruited to HIV-1 preintegration complex, through a mechanism yet to be elucidated.
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Details
- Title
- Drug 9AA reactivates p21/Waf1 and Inhibits HIV-1 progeny formation
- Creators
- Weilin Wu - Washington University Medical CenterKylene Kehn-Hall - George Washington UniversityCaitlin Pedati - Washington University Medical CenterLynnsey Zweier - George Washington UniversityIris Castro - George Washington UniversityZachary Klase - George Washington UniversityCynthia S Dowd - George Washington UniversityLarisa Dubrovsky - George Washington UniversityMichael Bukrinsky - George Washington UniversityFatah Kashanchi - George Washington University
- Publication Details
- Virology journal, v 5(1), pp 41-41
- Publisher
- BioMed Central
- Number of pages
- 1
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000255476500001
- Scopus ID
- 2-s2.0-42249093865
- Other Identifier
- 991021902598104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology