p73 interacts with human immunodeficiency virus type 1 Tat in astrocytic cells and prevents its acetylation on lysine 28

Shohreh Amini, Giuseppe Mameli, Luis Del Valle, Anna Skowronska, Krzysztof Reiss, Benjamin Gelman, Martyn K. White, Kamel Khalili, Bassel E. Sawaya

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32 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat is a potent transcriptional activator of the HIV-1 promoter and also has the ability to modulate a number of cellular regulatory circuits including apoptosis. Tat exerts its effects through interaction with viral as well as cellular proteins. Here, we studied the influence of p73, a protein that is implicated in apoptosis and cell cycle control, on Tat functions in the central nervous system. Protein interaction studies using immunoprecipitation followed by Western blot and glutathione 5-transferase pull-down assays demonstrated the association of Tat with p73. Tat bound to the N-terminal region of p73 spanning amino acids 1 to 120, and this interaction required the cysteine-rich domain (amino acids 30 to 40) of Tat. Association of p73 with Tat prevented the acetylation of Tat on lysine 28 by PCAF. Functional studies including RNA interference showed that p73 inhibited Tat stimulation of the HIV-1 promoter. Furthermore, p73 prevented the interaction of Tat with cyclin T1 in vitro but not in vivo. These findings suggest possible new therapeutic approaches, using p73, for Tat-mediated AIDS pathogenesis.

Original languageEnglish (US)
Pages (from-to)8126-8138
Number of pages13
JournalMolecular and Cellular Biology
Volume25
Issue number18
DOIs
StatePublished - Sep 2005

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Amini, S., Mameli, G., Del Valle, L., Skowronska, A., Reiss, K., Gelman, B., White, M. K., Khalili, K., & Sawaya, B. E. (2005). p73 interacts with human immunodeficiency virus type 1 Tat in astrocytic cells and prevents its acetylation on lysine 28. Molecular and Cellular Biology, 25(18), 8126-8138. https://doi.org/10.1128/MCB.25.18.8126-8138.2005