P-TEFb and Brd4 in HIV-1 transcription and latency
Min Liu
University of California, Berkeley
Basic Biomedical Sciences
2010
Accumulating evidence has implicated the bromodomain protein Brd4 as a chromatin adapter for recruiting P-TEFb, a general transcription factor that stimulates the elongation of RNA polymerase II, to diverse gene promoters. Although generally required for transcription including basal HIV-1 transcription that is key at the onset of latency activation, Brd4 is unnecessary and even prohibitive for HIV transcription activated by the viral encoded Tat protein due to its competition with Tat for binding to P-TEFb. Proposed here are experiments to further examine the role for the Brd4-P-TEFb complex in controlling HIV-1 transcription and reactivation from latency. Efforts will also be directed toward the elucidation of the mechanism that promotes the Brd4-P-TEFb interaction with a special emphasis on a possible role for Brd4 phosphorylation in this process. As the reactivation of latently infected HIV-1 that can be subsequently cleared by Highly Active Antiretroviral Therapy (HAART) holds great promise toward finding a real cure for HIV/AIDS, the proposed experiments may reveal novel targets and suggest innovative means to eradicate latent HIV-1 reservoirs in infected patients.
