HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 44, 46046-46056, October 29, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/44/46046    most recent M403792200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions 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. Social Bookmarking                      What's this?

Interplay between HIV-1 Vpr and Sp1 Modulates p21^WAF1 Gene Expression in Human Astrocytes^*

Shohreh Amini, Marcus Saunders, Kimberly Kelley, Kamel Khalili, and Bassel E. Sawaya

From the Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122

The Vpr (viral protein R) of human immunodeficiency virus, type 1, which is expressed during the late stage of the viral infection, has received special attention because of its ability to control transcription of the human immunodeficiency virus, type 1, long terminal repeat and to influence cell cycle progression. Here we demonstrate that Vpr has the ability to regulate transcription of the cyclin-dependent kinase inhibitor, p21^WAF1 (p21), one of the key regulators of the cell cycle, in human astrocytic cells. The results from transcription assays demonstrated that Vpr augments promoter activity of p21 through the GC-rich region located between nucleotides -84 and -74 with respect to the +1 transcription start site. Activation of p21 by Vpr required cooperativity of Sp1, which binds to the DNA sequence spanning -84 to -74. Results from bandshift assay revealed an increased level of Sp1 DNA binding activity in the presence of Vpr. Furthermore, Vpr was able to associate with Sp1 via the zinc finger domain located in the C-terminal region of Sp1. Functional studies revealed that the cooperativity between Vpr and Sp1 requires the zinc finger domain at the C terminus and the glutamine-rich domain at the N terminus of Sp1. Expression of p53 further enhanced the level of Vpr-Sp1-mediated transcription activation of p21 through the sequence spanning -84 to -74 and increased the DNA binding activity of Sp1 in the presence of Vpr. Results from glutathione S-transferase pull-down assay showed the association of Vpr with p53 in extracts containing Sp1. Altogether, the outcome of our functional and binding studies suggested that the physical interaction of Vpr with Sp1 and p53 could modulate transcriptional activity of p21.

Received for publication, April 5, 2004 , and in revised form, July 13, 2004.

^* This work was supported by National Institutes of Health grants (to K. Khalili, S. A., and B. E. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Center for Neurovirology and Cancer Biology, Temple University, 1900 N 12th St. (015-96), Philadelphia, PA 19122. Tel.: 215-204-0607; Fax: 215-204-0679; E-mail: sawaya{at}temple.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. N. Harman, M. Kraus, C. R. Bye, K. Byth, S. G. Turville, O. Tang, S. K. Mercier, N. Nasr, J. L. Stern, B. Slobedman, et al. HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase Blood, July 2, 2009; 114(1): 85 - 94. [Abstract] [Full Text] [PDF]

				S. L. Deshmane, R. Mukerjee, S. Fan, L. Del Valle, C. Michiels, T. Sweet, I. Rom, K. Khalili, J. Rappaport, S. Amini, et al. Activation of the Oxidative Stress Pathway by HIV-1 Vpr Leads to Induction of Hypoxia-inducible Factor 1{alpha} Expression J. Biol. Chem., April 24, 2009; 284(17): 11364 - 11373. [Abstract] [Full Text] [PDF]

				Y. K. Oh, H. J. Lee, M.-H. Jeong, M. Rhee, J.-W. Mo, E. H. Song, J.-Y. Lim, K.-H. Choi, I. Jo, S. I. Park, et al. Role of Activating Transcription Factor 3 on TAp73 Stability and Apoptosis in Paclitaxel-Treated Cervical Cancer Cells Mol. Cancer Res., July 1, 2008; 6(7): 1232 - 1249. [Abstract] [Full Text] [PDF]

				G. Mameli, S. L. Deshmane, M. Ghafouri, J. Cui, K. Simbiri, K. Khalili, R. Mukerjee, A. Dolei, S. Amini, and B. E. Sawaya C/EBPbeta regulates human immunodeficiency virus 1 gene expression through its association with cdk9 J. Gen. Virol., February 1, 2007; 88(2): 631 - 640. [Abstract] [Full Text] [PDF]

				A. Rossi, R. Mukerjee, P. Ferrante, K. Khalili, S. Amini, and B. E. Sawaya Human immunodeficiency virus type 1 Tat prevents dephosphorylation of Sp1 by TCF-4 in astrocytes J. Gen. Virol., June 1, 2006; 87(6): 1613 - 1623. [Abstract] [Full Text] [PDF]

				W.-H. Kim, J. W. Lee, Y. H. Suh, S. H. Hong, J. S. Choi, J. H. Lim, J. H. Song, B. Gao, and M. H. Jung Exposure to Chronic High Glucose Induces {beta}-Cell Apoptosis Through Decreased Interaction of Glucokinase With Mitochondria: Downregulation of Glucokinase in Pancreatic {beta}-Cells Diabetes, September 1, 2005; 54(9): 2602 - 2611. [Abstract] [Full Text] [PDF]