title: Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein.
abstract: HIV-1 encodes a potent trans-activator protein, tat, which is essential for viral gene expression. To study tat domains that function in trans-activation, we chemically synthesized the 86 amino acid tat protein (tat-86) and tat mutant peptides. Remarkably, tat-86 is rapidly taken up by cells, and produces a massive and specific stimulation of HIV-LTR-driven RNA synthesis. Mutant peptides of 21 to 41 amino acids exhibit significant activity. Only two regions are essential for trans-activation; we suggest that one represents an activation region and the other, a nucleic acid binding or nuclear targeting region. Amino acid substitutions within these regions greatly reduce trans-activation, demonstrating the functional significance of these domains. The N-terminal 37 amino acids and exon 2 are not essential. Thus, tat is similar to regulatory proteins of Ad E1A and BPV1 E5 oncogenes, requiring only small domains for autonomous function.
authors.affiliation: Institute for Molecular Virology, St. Louis University School of Medicine, Missouri 63110.
authors.forename: M
authors.initials: M
authors.lastname: Green
authors.forename: P M
authors.initials: PM
authors.lastname: Loewenstein
mesh_terms: D000595:Amino Acid Sequence; D002872:Chromosome Deletion; D005786:Gene Expression Regulation; D015696:Gene Products, tat; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D008845:Microinjections; D009154:Mutation; D009857:Oncogenes; D012367:RNA, Viral / Q000096:biosynthesis; D014157:Transcription Factors / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D012367:RNA, Viral; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus