title: Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T.
abstract: The transcriptional transactivator Tat from HIV binds to the transactivation response element (TAR) RNA to increase rates of elongation of viral transcription. Human cyclin T supports these interactions between Tat and TAR. In this study, we report the sequence of mouse cyclin T and identify the residues from positions 1 to 281 in human cyclin T that bind to Tat and TAR. Mouse cyclin T binds to Tat weakly and is unable to facilitate interactions between Tat and TAR. Reciprocal exchanges of the cysteine and tyrosine at position 261 in human and mouse cyclin T proteins also render human cyclin T inactive and mouse cyclin T active. These findings reveal the molecular basis for the restriction of Tat transactivation in rodent cells.
authors.affiliation: Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, CA 94143-0703, USA.
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
authors.forename: R
authors.initials: R
authors.lastname: Taube
authors.forename: J
authors.initials: J
authors.lastname: Wimmer
authors.forename: T P
authors.initials: TP
authors.lastname: Cujec
authors.forename: B M
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D006224:Cricetinae; D056906:Cyclin T; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine; D015696:Gene Products, tat / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine