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Journal of Virology, March 2001, p. 2314-2323, Vol. 75, No. 5
Department of Microbiology and
Immunology1 and Department of Internal
Medicine, Division of Infectious Diseases,2
University of Michigan Medical Center, Ann Arbor, Michigan
48109-0640; Laboratory of Biochemistry and Molecular Biology,
Rockefeller University, New York, New York
100213; Harvard AIDS Institute,
Department of Immunology and Infectious Diseases, Harvard School of
Public Health, Boston, Massachusetts 021154; and
Howard Hughes Medical Institute6 and
Skirball Institute of Biomolecular Medicine, New York University
Medical Center, New York, New York 100165
Received 1 March 2000/Accepted 7 December 2000
Zinc finger-containing GLI proteins are involved in the development
of Caenorhabditis elegans, Xenopus, Drosophila, zebrafish, mice, and humans. In this study, we show that an isoform of human GLI-2
strongly synergizes with the Tat transactivating proteins of human
immunodeficiency virus types 1 and 2 (HIV-1 and -2) and markedly
stimulates viral replication. GLI-2 also synergizes with the previously
described Tat cofactor cyclin T1 to stimulate Tat function.
Surprisingly, GLI-2/Tat synergy is not dependent on either a typical
GLI DNA binding site or an intact Tat activation response element but
does require an intact TATA box. Thus, GLI-2/Tat synergy results from a
mechanism of action which is novel both for a GLI protein and for a Tat
cofactor. These findings link the GLI family of transcriptional and
developmental regulatory proteins to Tat function and HIV replication.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2314-2323.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Human GLI-2 Is a Tat Activation Response
Element-Independent Tat Cofactor
*
Corresponding author. Mailing address: 5220 MSRB III,
1150 W. Medical Center Dr., Ann Arbor, MI 48109-0640. Phone: (734)
647-1786. Fax: (734) 764-0101. E-mail: Dmarkov{at}umich.edu.
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