AP-1 RECOGNIZES SEQUENCE ELEMENTS ON HIV-1 LTR IN HUMAN EPITHELIAL TUMOR-CELL LINES

Investigation of the nucleotide sequence of the HIV-1 LTR showed the p resence of four novel short DNA regions which are homologous to the re cognition site for the cellular transcription factor AP-1. Four short oligonucleotide hybrids containing these potential AP-1 sites were con structed and used in gel retardation assays and in competition experim ents in order to determine the role of the AP-L protein in the regulat ion of HIV-1 expression. The breast MDA MB 468 and cervical HeLa turne r cell lines, which are known to overexpress the AP-1 protein were use d in a gel retardation assay as a control to study the affinity of the AP-1 to synthesized oligonucleotide sequences. We have observed speci fic binding of nuclear factor AP-1 to three of these oligonucleotide h ybrids. These results demonstrate the presence of three novel AP-1 bin ding sites on HIV-1 LTR, one of which was found within the TAR element and in the Tat protein binding region. Moreover, they suggest that AP -1 could be contributing to HIV-1 transcriptional regulation through i ts interaction with the AP-1 binding sites of HIV-1 LTR.