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 identified as the region of Rb required for binding to oncoproteins from DNA tumour viruses(1,2), which disrupt the binding of Rb to the E2F family 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 transcription. Here we report that Rb is selectively recruited to promoters through E2F, where it in turn inactivates surrounding transcription factors by blocking their interaction with the basal transcription complex. We suggest that this repressor activity is essential for inhibiting promoters that contain enhancers in addition to E2F sites.