Regulation of HTLV-I gene expression by tax and AP-2.
The HTLV-I transactivator protein tax activates expression of both viral and cellular genes. In addition it has been demonstrated to repress expression of the DNA beta-polymerase gene. We wished to investigate potential interactions between tax and the cellular transcription factor AP-2 which binds to distinct motifs in each of the three 21-bp repeat sequences in the HTLV-I LTR. First we demonstrate that AP-2 is capable of activating HTLV-I gene expression. Cotransfection experiments reveal that AP-2 and tax are capable of inhibiting each other's ability to activate HTLV-I gene expression. The mechanism of this inhibition was studied by gel retardation analysis using both bacterial and in vitro synthesized AP-2 and tax proteins. These results indicate that tax inhibits the ability of AP-2 to bind to the 21-bp repeat. Mutational analysis of both tax and AP-2 demonstrate that the amino termini of both proteins are potential sites of interaction. These results are consistent with a model in which AP-2 and tax can potentially form protein complexes resulting in an altered ability of each factor to modulate HTLV-I gene expression.
Muchardt
C
C
Department of Medicine, Southwestern Medical School, Dallas, TX 75235.
Seeler
J S
JS
Gaynor
R B
RB
D001483:Base Sequence; D001665:Binding Sites; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016356:Gene Products, tax / Q000378:metabolism / Q000494:pharmacology; D005814:Genes, Viral; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D050656:Transcription Factor AP-2; D014157:Transcription Factors