This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amini, S. Articles by Sawaya, B. E. Search for Related Content PubMed PubMed Citation Articles by Amini, S. Articles by Sawaya, B. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2005, p. 8126-8138, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8126-8138.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

p73 Interacts with Human Immunodeficiency Virus Type 1 Tat in Astrocytic Cells and Prevents Its Acetylation on Lysine 28

Shohreh Amini,¹ Giuseppe Mameli,² Luis Del Valle,² Anna Skowronska,² Krzysztof Reiss,² Benjamin B. Gelman,³ Martyn K. White,² Kamel Khalili,² and Bassel E. Sawaya^2*

Center for Neurovirology, and,¹ Center for Neurovirology, Department of Neuroscience, School of Medicine, Temple University, 1900 North 12th Street, 015-96, Philadelphia, Pennsylvania 19122, and,² Texas Center for NeuroAIDS Research, Department of Pathology, University of Texas Medical Branch at Galveston, Rt. 0785, Galveston, Texas 77555-0785³

Received 18 January 2005/ Returned for modification 16 March 2005/ Accepted 14 June 2005

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 S-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.

---

* Corresponding author. Mailing address: Center for Neurovirology and Cancer Biology, Temple University, 1900 North 12th Street (015-96), Philadelphia, PA 19122. Phone: (215) 204-0607. Fax: (215) 204-0679. E-mail: sawaya{at}temple.edu.

---

Molecular and Cellular Biology, September 2005, p. 8126-8138, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8126-8138.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Basile, A., Darbinian, N., Kaminski, R., White, M. K., Gentilella, A., Turco, M. C., Khalili, K. (2009). Evidence for modulation of BAG3 by polyomavirus JC early protein. J. Gen. Virol. 90: 1629-1640 [Abstract] [Full Text]  
• Rossi, A., Mukerjee, R., Ferrante, P., Khalili, K., Amini, S., Sawaya, B. E. (2006). Human immunodeficiency virus type 1 Tat prevents dephosphorylation of Sp1 by TCF-4 in astrocytes. J. Gen. Virol. 87: 1613-1623 [Abstract] [Full Text]  
• Aprea, S., Del Valle, L., Mameli, G., Sawaya, B. E., Khalili, K., Peruzzi, F. (2006). Tubulin-Mediated Binding of Human Immunodeficiency Virus-1 Tat to the Cytoskeleton Causes Proteasomal-Dependent Degradation of Microtubule-Associated Protein 2 and Neuronal Damage. J. Neurosci. 26: 4054-4062 [Abstract] [Full Text]