HUMAN RETINOBLASTOMA SUSCEPTIBILITY GENE PROMOTER IS POSITIVELY AUTOREGULATED BY ITS OWN PRODUCT

The product of the retinoblastoma susceptibility gene is a 1O5-kDa pro tein that has properties of a cell cycle regulatory factor. Previous r eports indicated that two distinct DNA-binding factors, RBF-1 and ATF, play an important part in the transcription of the human retinoblasto ma gene (Rb). Recently, we demonstrated that pRb activates expression of the human transforming growth factor-beta 2 gene through ATF-B Sinc e the human Rb gene promoter also contains an ATF-a-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 acti vity 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 dom ain of pRb is responsible for the Rb autoinduction through ATF-2. Rb a utoinduction may be important for maintaining the action of pRb during cell growth, and loss of autoinducibility may contribute to retinobla stoma.