RETINOBLASTOMA BINDING-FACTOR-1 SITE IN THE CORE PROMOTER REGION OF THE HUMAN RB GENE IS ACTIVATED BY HGABP E4TF1/

We previously reported two oncogenic point mutations present in the RE (retinoblastoma) gene promoter region, found at consensus Sp1 and ATF sites, respectively, and in two separate hereditary RE families, Howe ver, Sp1 protein was shown not to bind to the Sp1 site; this indicated that the Sp1 consensus site mutation was blocking the action of an al ternative transcription factor, which we called RBF-1 (retinoblastoma binding factor 1), Subsequent purification of RBF-1 revealed it to be hGABP/E4TF1, a transactivator from the adenovirus early-region 4 promo ter, In this study, we directly examined the effects of hGABP/E4TF1 on transactivation of the RB gene promoter through the RBF-1 site. As ex pected, hGABP/E4TF1 enhanced the core RE promoter activity, whereas it did not stimulate a mutant RBF-1 site. We therefore conclude that the most essential transcription factor in the human RE gene is likely to be hGABP/E4TF1.