A single Cys706 to Phe substitution in the retinoblastoma protein causes the loss of binding to SV40 T antigen

Cell Growth Differ. 1990 Dec;1(12):647-51.


Most naturally occurring mutants of the retinoblastoma (RB) protein contain large deletions or truncations. The small cell lung carcinoma cell line H209 contains a normal-sized but unphosphorylated RB protein (Hensel et al., Cancer Res., 50: 3067-3072, 1990), which fails to form a complex with SV40 T antigen, suggesting that the RB gene of H209 may contain a subtle mutation. To define this mutation, the RB complementary DNA and genomic DNA were sequenced, revealing a point mutation in exon 21 that changed a G to a T. This results in an amino acid substitution of a Phe for Cys706. The mutant RB complementary DNA was used as a template for in vitro transcription and translation to synthesize the mutated protein. The resulting protein failed to bind to SV40 T antigen, demonstrating that a single missense mutation of the RB gene led to the complete inactivation of the ability of the RB protein to bind T antigen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Polyomavirus Transforming / metabolism*
  • Base Sequence
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Protein Binding / genetics
  • Retinoblastoma Protein / genetics*
  • Retinoblastoma Protein / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Antigens, Polyomavirus Transforming
  • Retinoblastoma Protein