The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element.
The retinoblastoma susceptibility gene product, Rb, is suspected to suppress cell growth. Rb is a 110-114 kd nuclear phosphoprotein. We have previously demonstrated that SV40 T antigen binds only to unphosphorylated Rb, and not pp112-114Rb, the family of phosphorylated Rb. Here we demonstrate the cell cycle-dependent phosphorylation of Rb. In G0/G1 cells, virtually all the Rb is unphosphorylated. In contrast, during S and G2, it is largely, if not exclusively, phosphorylated. Rb phosphorylation occurs at the G1/S boundary in several cell types tested. A 14 residue peptide, corresponding to the SV40 T domain required for transformation, is able to compete effectively with SV40 T for binding to p110Rb. We propose a model to explain how Rb may suppress cell growth by acting as a cell cycle regulatory element.
DeCaprio
J A
JA
Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Ludlow
J W
JW
Lynch
D
D
Furukawa
Y
Y
Griffin
J
J
Piwnica-Worms
H
H
Huang
C M
CM
Livingston
D M
DM
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000166:cytology; D005134:Eye Neoplasms / Q000235:genetics*; D005809:Genes, Regulator; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D010750:Phosphoproteins / Q000302:isolation & purification / Q000502:physiology*; D010766:Phosphorylation; D012175:Retinoblastoma / Q000235:genetics*; D016160:Retinoblastoma Protein; D013489:Suppression, Genetic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D010750:Phosphoproteins; D016160:Retinoblastoma Protein; D006918:Hydroxyurea