Abstract
The human immunodeficiency virus type 1 (HIV-1) encodes a potent transactivator, Tat, which functions through binding to a short leader RNA, called transactivation responsive element (TAR). Recent studies suggest that Tat activates the HIV-1 long terminal repeat (LTR), mainly by adapting co-activator complexes, such as p300, PCAF and the positive transcription elongation factor P-TEFb, to the promoter. Here, we show that the proto-oncoprotein Hdm2 interacts with Tat and mediates its ubiquitination in vitro and in vivo. In addition, Hdm2 is a positive regulator of Tat-mediated transactivation, indicating that the transcriptional properties of Tat are stimulated by ubiquitination. Fusion of ubiquitin to Tat bypasses the requirement of Hdm2 for efficient transactivation, supporting the notion that ubiquitin has a non-proteolytic function in Tat-mediated transactivation.
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Acknowledgements
We wish to thank O. Bensaude and J. Piette for helpful discussions, B. Réant for technical assistance, H. Neel and J. Piette for the gift of Hdm2 expression plasmid, D. Trouche for HA-p53 plasmid, R. Kopito for pHis–Ub and pHis–UBK48R, R. Benarous for anti-βTrCP antibody. This work was supported by grants from the Agence Nationale de Recherche sur le SIDA (ANRS), Human Frontier Science Program, Minister de la Recherche (ACI) to M.B., by Agence de Recherche contre le Cancer (ARC), ANRS and SIDACTION (S.E.), by CNRS and ARC (O.C), by the German-Israeli Foundation for Scientific Research and Development (M.S.) and by the European Commission (QLGI-CT-2001-02026) to M.S and O.C. R.K. was supported by ANRS–SIDACTION, O.P. by a ARC post-doctoral fellowship and V.B. by a MERT scholarship.
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Brès, V., Kiernan, R., Linares, L. et al. A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter. Nat Cell Biol 5, 754–761 (2003). https://doi.org/10.1038/ncb1023
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DOI: https://doi.org/10.1038/ncb1023
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