Ras-responsiveness of the HIV-1 LTR requires RBF-1 and RBF-2 binding sites.
Lentiviruses characteristically form latent integrated proviruses whose transcription can be induced by cell regulatory signals. The HIV-1 LTR responds to multiple signals, including the Ras pathway. We report here that Ras-responsive HIV-1 transcription requires two previously undescribed factors, RBF-1 and RBF-2 in Jurkat T cells. RBF-1 binds to Ets-like motifs located between nucleotides -151 and -142, and within the NF-kappaB binding sites, but is distinct from Ets-1 or Elf-1. RBF-2 binds the HIV-1 LTR at nucleotides -131 and -121 and immediately 3' of the TATA box. Both RBF-1 and RBF-2 contain DNA binding subunits of relative molecular weight 100 kilodaltons. Mutation of the RBF-1 and RBF-2 binding elements (RBEs) prevents Ras stimulation of HIV-1 LTR-directed transcription. These data define a mechanism for Ras responsiveness of HIV-1 transcription that involves the previously uncharacterized factors RBF-1 and RBF-2.
Bell
B
B
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver.
Sadowski
I
I
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D014157:Transcription Factors