MECHANISM OF ACTIVE TRANSCRIPTIONAL REPRESSION BY THE RETINOBLASTOMA PROTEIN

THE retinoblastoma tumour-suppressor protein (Rb) belongs to a family that share a motif known as the pocket. The pocket was originally iden tified as the region of Rb required for binding to oncoproteins from D NA tumour viruses(1,2), which disrupt the binding of Rb to the E2F fam ily of cell-cycle transcription factors (referred to collectively here as E2F)(3). Rb switches E2F sites from positive to negative elements( 4), suggesting that Rb-E2F is an active complex that blocks transcript ion. Here we report that Rb is selectively recruited to promoters thro ugh E2F, where it in turn inactivates surrounding transcription factor s by blocking their interaction with the basal transcription complex. We suggest that this repressor activity is essential for inhibiting pr omoters that contain enhancers in addition to E2F sites.