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Drug 9AA reactivates p21/Waf1 and Inhibits HIV-1 progeny formation

Virology Journal
Springer (Biomed Central Ltd.)
Publication Date
DOI: 10.1186/1743-422x-5-41
  • Research
  • Chemistry
  • Medicine

Abstract ral ss BioMed CentVirology Journal Open AcceResearch Drug 9AA reactivates p21/Waf1 and Inhibits HIV-1 progeny formation Weilin Wu1, Kylene Kehn-Hall1, Caitlin Pedati1, Lynnsey Zweier1, Iris Castro1, Zachary Klase1, Cynthia S Dowd2, Larisa Dubrovsky1, Michael Bukrinsky1 and Fatah Kashanchi*1,3,4 Address: 1The George Washington University Medical Center, Department of Biochemistry and Molecular Biology, Washington, DC 20037, USA, 2The George Washington University, Department of ChemistryWashington, DC 20037, USA, 3The Institute for Genomic Research, Rockville, MD 20850, USA and 4The George Washington University, W.M. Keck Institute for Proteomics Technology and Applications, Washington, DC 20037, USA Email: Weilin Wu - [email protected]; Kylene Kehn-Hall - [email protected]; Caitlin Pedati - [email protected]; Lynnsey Zweier - [email protected]; Iris Castro - [email protected]; Zachary Klase - [email protected]; Cynthia S Dowd - [email protected]; Larisa Dubrovsky - [email protected]; Michael Bukrinsky - [email protected]; Fatah Kashanchi* - [email protected] * Corresponding author 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

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