title: A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter.
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.
authors.affiliation: Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Brès
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Kiernan
authors.forename: Laetitia K
authors.initials: LK
authors.lastname: Linares
authors.forename: Christine
authors.initials: C
authors.lastname: Chable-Bessia
authors.forename: Olga
authors.initials: O
authors.lastname: Plechakova
authors.forename: Céline
authors.initials: C
authors.lastname: Tréand
authors.forename: Stephane
authors.initials: S
authors.lastname: Emiliani
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Peloponese
authors.forename: Kuan-Teh
authors.initials: KT
authors.lastname: Jeang
authors.forename: Olivier
authors.initials: O
authors.lastname: Coux
authors.forename: Martin
authors.initials: M
authors.lastname: Scheffner
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
mesh_terms: D002460:Cell Line; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D054322:tat Gene Products, Human Immunodeficiency Virus; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2