title: Interactions between Tat of HIV-2 and transcription factor Sp1.
abstract: Tat of HIV-2 (Tat-2) requires host cellular factors for optimal function. We show that transactivation by Tat-2 of the HIV promoter requires cis-acting binding sites for Sp1 or Sp1 brought to the promoter via a heterologous system. We demonstrate that an activation domain in Tat-2 consists of one of two potential alpha-helices in the amino-terminal region, the cysteine-rich region, and the core region and that this independent activation domain requires cis-acting Sp1-binding sites for function. Tat-2 interacts with Sp1 in in vitro binding assays, and these interactions require basic residues outside of the Tat-2 activation domain. The regions in Sp1 sufficient for functional synergy with Tat are the Sp1 activation domains, while the DNA-binding region is dispensable. Substitution mutations of a glutamine-rich region in one Sp1 activation domain, which eliminate interactions with a TBP-associated factor, also significantly decrease synergy with Tat. Thus, the functional synergy between Tat-2 and Sp1 localizes to domains in each activator that interact with components of the transcription complex. We suggest that these interactions, rather than direct Tat/Sp1 binding, result in highly processive RNA polymerase II complexes and full-length viral transcripts.
authors.affiliation: Department of Medicine, Veterans Administration Medical Center, San Francisco, California, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Pagtakhan
authors.forename: S E
authors.initials: SE
authors.lastname: Tong-Starksen
mesh_terms: D001665:Binding Sites; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D016329:Sp1 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus