Letter abstract
Nature Cell Biology 5, 754 - 761 (2003)
Published online: 27 July 2003 | doi:10.1038/ncb1023
A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter
Vanessa Brès1,6, Rosemary E. Kiernan1,6, Laetitia K. Linares2, Christine Chable-Bessia1, Olga Plechakova3, Céline Tréand4, Stephane Emiliani4, Jean-Marie Peloponese5, Kuan-Teh Jeang5, Olivier Coux3, Martin Scheffner2 & Monsef Benkirane1
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.
- Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France.
- Zentrum für Biochemie, Universität zu Köln, Köln 50931, Germany.
- Centre de Recherche de Biochimie Macromoleculaire, UPR1086, Montpellier, France.
- Institut Cochin, Departement des Maladies Infectieuses, Paris 75014, France.
- Laboratory of Molecular Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
- These authors contributed equally to this work.
Correspondence to: Monsef Benkirane1 e-mail: bmonsef@igh.cnrs.fr
