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Figure 7 | Virology Journal

Figure 7

From: 9-aminoacridine Inhibition of HIV-1 Tat Dependent Transcription

Figure 7

Model of 9AA induced activation of p21WAF1 in HIV-1 infected cells. In HIV-1 infected cells, p53 is inactivated through the binding to Tat. Upon 9AA treatment, p53 becomes phosphorylated at Ser15, resulting in loss of Tat binding and transcription of p53 dependent promoters, specifically p21WAF1. p21WAF1 protein levels are increased and this newly formed p21WAF1 is able to bind to both cycT/cdk9 and cycE/cdk2 complexes. Binding of p21WAF1 to cyclin/cdk complexes results in inhibition of HIV-1 LTR transcription possibly through decreased RNA Pol II and/or histone H1 phosphorylation. p21WAF1 can also be activated by 9AA treatment in p53 mutant cells by a yet undefined mechanism.

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