Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase

EMBO J. 1991 Apr;10(4):857-64.


The retinoblastoma gene product (RB) is a nuclear protein which has been shown to function as a tumor suppressor. It is phosphorylated from S to M phase of the cell cycle and dephosphorylated in G1. This suggests that the function of RB is regulated by its phosphorylation in the cell cycle. Ten phosphotryptic peptides are found in human RB proteins. The pattern of RB phosphorylation does not change from S to M phases of the cell cycle. Hypophosphorylated RB prepared from insect cells infected with an RB-recombinant baculovirus is used as a substrate for in vitro phosphorylation reactions. Of several protein kinases tested, only cdc2 kinase phosphorylates RB efficiently and all 10 peptides can be phosphorylated by cdc2 in vitro. Removal of cdc2 from mitotic cell extracts by immunoprecipitation causes a concomitant depletion of RB kinase activity. These results indicate that cdc2 or a kinase with similar substrate specificity is involved in the cell cycle-dependent phosphorylation of the RB protein.

Publication types

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

MeSH terms

  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle*
  • Cell Line
  • Genes, Retinoblastoma*
  • HeLa Cells / cytology
  • HeLa Cells / metabolism
  • Humans
  • Mitosis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptide Mapping
  • Phosphopeptides / isolation & purification
  • Phosphorylation
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*


  • Nuclear Proteins
  • Phosphopeptides
  • Retinoblastoma Protein
  • CDC2 Protein Kinase