TRANSCRIPTIONAL INHIBITION BY THE RETINOBLASTOMA PROTEIN

The retinoblastoma protein, pRB, appears to play a key role in coordin ating the regulation of cell cycle position and transcriptional events . pRB undergoes specific cell-cycle-dependent phosphorylation, being u nderphosphorylated in G1 and heavily phosphorylated in S, G2, and M. T he underphosphorylated form is able to interact with the E2F transcrip tion factor. Recently, we have cloned a cDNA for E2F-1. By using this clone and a series of non-pRB binding mutants, we have been able to sh ow that the binding of pRB to E2F-1 causes inhibition of E2F-mediated transactivation. pRB's inhibition of E2F-mediated transcription would be lost by mutation in the retinoblastoma gene in human tumours, by pR B's interaction with DNA tumour virus oncoproteins, or by phosphorylat ion during the cell cycle.