Inactivation of oncoprotein binding by a single Cys-to-Tyr substitution in the retinoblastoma protein

We previously found a new single amino acid substitution at codon 706 (Cys-to-Tyr) of the retinoblastoma (RB) gene in a sporadic retinoblastoma patient. The glutathione S-transferase-RB fused protein containing this mutation was here tested for binding to SV40 large T antigen and adenovirus E1A protein, and was shown to have lost its binding affinity. Thus, Tyr, as well as Phe, residues substituted for Cys⁷⁰⁶ were found to abolish the RB protein activity.