title: Interactions between equine cyclin T1, Tat, and TAR are disrupted by a leucine-to-valine substitution found in human cyclin T1.
abstract: Transcriptional transactivators (Tat) from human immunodeficiency and equine infectious anemia viruses (HIV and EIAV) interact with their transactivation response elements (TAR) to increase the rates of viral transcription. Whereas the human cyclin T1 is required for the binding of Tat to TAR from HIV, it is unknown how Tat from EIAV interacts with its TAR. Furthermore, Tat from EIAV functions in equine and canine cells but not in human cells. In this study, we present sequences of cyclins T1 from horse and dog and demonstrate that their N-terminal 300 residues rescue the transactivation of Tat from EIAV in human cells. Although human and equine cyclins T1 bind to this Tat, only the equine cyclin T1 supports the binding of Tat to TAR from EIAV. Finally, a reciprocal exchange of the valine for the leucine at position 29 in human and equine cyclins T1, respectively, renders the human cyclin T1 active and the equine cyclin T1 inactive for Tat transactivation from EIAV. Thus, the collaboration between a specific cyclin T1 and Tat for their high-affinity interaction with TAR is a common theme of lentiviral transactivation.
authors.affiliation: Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, California 94143-0703, USA.
authors.forename: R
authors.initials: R
authors.lastname: Taube
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
authors.forename: D
authors.initials: D
authors.lastname: Irwin
authors.forename: J
authors.initials: J
authors.lastname: Wimmer
authors.forename: M
authors.initials: M
authors.lastname: Geyer
authors.forename: B M
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D056906:Cyclin T; D016213:Cyclins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004285:Dogs; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006736:Horses; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics* / Q000378:metabolism; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020218:Response Elements; D017386:Sequence Homology, Amino Acid; D020079:Terminal Repeat Sequences; D015533:Transcriptional Activation; D014633:Valine / Q000235:genetics / Q000378:metabolism
chemical_list: C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D007930:Leucine; D014633:Valine