THE TRANSCRIPTION FACTOR E2F-1 MEDIATES THE AUTOREGULATION OF RB GENE-EXPRESSION

The retinoblastoma (RB) gene is the prototype tumor suppressor gene. M utations in this gene are often associated with the occurrence of vari ous tumors. Several mutations have been found in the promoter region o f the gene, suggesting that inappropriate transcriptional regulation o f the R-B gene contributes to tumorigenesis. Sequence analysis of the RB promoter has revealed a potential E2F recognition site within a reg ion critical for RB gene transcription. By using the cloned E2F-1 gene , here we report that (i) RB expression is negatively regulated by its own gene product, (ii) E2F-1 binds specifically to an E2F recognition sequence in the RB promoter and transactivates the RB promoter, (iii) overexpression of RB suppresses E2F-1-mediated stimulation of RB prom oter activity, and (iv) the expression of the RB gene is paralleled by the expression of the E2F-1 gene during cell cycle progression. These results demonstrate that expression of RB is negatively autoregulated through E2F-1.