The human retinoblastoma susceptibility gene promoter is positively autoregulated by its own product

The product of the retinoblastoma susceptibility gene is a 105-kDa protein that has properties of a cell cycle regulatory factor. Previous reports indicated that two distinct DNA-binding factors, RBF-1 and ATF, play an important part in the transcription of the human retinoblastoma gene (Rb). Recently, we demonstrated that pRb activates expression of the human transforming growth factor-β2 gene through ATF-2. Since the human Rb gene promoter also contains an ATF-2-like binding site, we examined whether pRb can regulate its own expression through ATF-2. Here we report that overexpression of Rb stimulates Rb promoter activity through the ATF binding site in a variety of different cell types. Mutation of the ATF binding site of the Rb promoter abolishes the Rb autoinduction. We have also determined that the carboxyl-terminal domain of pRb is responsible for the Rb autoinduction through ATF-2. Rb autoinduction may be important for maintaining the action of pRb during cell growth, and loss of autoinducibility may contribute to retinoblastoma.