Identification of a Growth Suppression Domain Within the Retinoblastoma Gene Product

To date, all naturally occurring retinoblastoma susceptibility gene (RB) mutations known to be compatible with stable protein expression map to the T/E1A and cellular protein-binding region (the "pocket" domain). This domain extends from residue 379 to 792. When full-length RB and certain truncated forms were synthesized in human RB -/- cells, we found that the minimal region necessary for overt growth suppression extended from residue 379 to 928. A functional pocket domain and sequences extending from the carboxy-terminal boundary of the pocket to the carboxyl terminus of the protein were both necessary for growth suppression. Both sets of sequences were also required for E2F binding; hence, the two functions may be linked.