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Journal of Virology, October 1998, p. 8252-8256, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Interaction of Human Immunodeficiency Virus Type 1 Tat with the Transcriptional Coactivators p300 and CREB Binding Protein

Michael O. Hottiger and Gary J. Nabel*

Departments of Internal Medicine and Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0650

Received 23 March 1998/Accepted 8 July 1998

Human immunodeficiency virus type 1 (HIV-1) encodes the transactivator protein Tat, which is essential for viral replication and progression to disease. Here we demonstrate that transcriptional activation by HIV-1 Tat involves p300 or the related cellular transcriptional coactivator CREB binding protein (CBP). Tat transactivation was inhibited by the 12S form of the adenovirus E1A gene product, which inhibits p300 function, and this inhibition was independent of its effect on NF-kappa B transcription. A biochemical interaction of p300 with Tat was demonstrated in vitro and in vivo by coimmunoprecipitation. The carboxy-terminal region of p300, which binds to E1A, was shown to bind specifically to the highly conserved basic domain of Tat, which also mediates binding to the Tat-responsive region RNA stem-loop structure. The ability of Tat to interact physically and functionally with this coactivator provides a mechanism to assemble a basal transcription complex which may subsequently respond to the effect of Tat on transcriptional elongation and represents a novel interaction between an RNA binding protein and a transcriptional coactivator.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, 1150 W. Medical Center Dr., 4520 MSRB I, Ann Arbor, MI 48109-0650. Phone: (734) 647-4798. Fax: (734) 647-4730. E-mail: gnabel{at}umich.edu.

Journal of Virology, October 1998, p. 8252-8256, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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