Canine cyclin T1 rescues equine infectious anemia virus tat trans-activation in human cells.
Human immunodeficiency virus-1 Tat protein and human Cyclin T1 mediate transcriptional activation by enhancing the elongation efficiency of RNA polymerase II. Activation of transcription of the related equine infectious anemia virus (EIAV) requires a similar protein known as eTat, which does not function in human cells. Expression of equine Cyclin T1 in human cells rescues eTat function, suggesting a general mechanism of transcription activation among lentiviruses. Here we present the cloning of Cyclin T1 from canine D17 osteosarcoma cells, which support EIAV transactivation, and show that canine Cyclin T1 confers eTat transactivation to human cells. A two-amino-acid change, from 79-proline-glycine-80 to 79-histidine-arginine-80, confers on the human Cyclin T1 the ability to cooperate with eTat in transcriptional activation. These findings suggested that the regions of Cyclin T1 that interact with lentiviral Tat proteins and TAR RNA elements form an extended domain, which very likely has a conserved fold.
Albrecht
T R
TR
Department of Genetics, Duke University Medical Center, Durham, North Carolina, 27710, USA.
Lund
L H
LH
Garcia-Blanco
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D056906:Cyclin T; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D020079:Terminal Repeat Sequences / Q000235:genetics; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; D012367:RNA, Viral