Journal of Virology, March 2001, p. 2314-2323, Vol. 75, No. 5
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2314-2323.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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.
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