The HIV-1 Tat transactivator protein: a therapeutic target?
The human immunodeficiency virus-1 (HIV-1), the causative agent of autoimmune deficiency syndrome (AIDS) is a major health problem world-wide. Central to HIV infection is the transactivator protein Tat, that plays a critical role in the nucleus during the HIV infectious cycle, by binding the transactivation-responsive region (TAR) and thereby enhancing transcriptional elongation. Tat appears to gain nuclear entry through a novel mechanism, independent of the normal cellular importin/Ran-dependent pathways, and regulated by a cytoplasmic retention mechanism. Since blocking Tat nuclear import is likely to prevent HIV infection, detailed delineation of Tat's nuclear import pathway is critical to assessing its viability as a therapeutic target. Other feasible anti-HIV therapies include approaches to inhibit Tat-TAR interaction.
Fulcher
Alex J
AJ
Dept. for Biochemistry and Mol. Biol., Monash University, Australia.
Jans
David A
DA
D016503:Drug Delivery Systems; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000378:metabolism*; D015696:Gene Products, tat / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009226:Myristates / Q000627:therapeutic use; D012367:RNA, Viral / Q000378:metabolism; D013498:Suramin / Q000627:therapeutic use; D013831:Thiamine / Q000627:therapeutic use; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D015696:Gene Products, tat; D009226:Myristates; C114528:O,O'-bismyristoyl thiamine disulfide; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D013498:Suramin; D013831:Thiamine