Regulation of retinoblastoma protein functions by ectopic expression of human cyclins.
The retinoblastoma susceptibility gene (RB) product, the retinoblastoma protein (pRb), functions as a regulator of cell proliferation. Introduction of the RB gene into SAOS-2 osteosarcoma cells, which lack functional pRb, prevents cell cycle progression. Such growth-suppressive functions can be modulated by phosphorylation of pRb, which occurs via cell cycle-regulated kinases. We show that constitutively expressed cyclins A and E can overcome pRb-mediated suppression of proliferation. pRb becomes hyperphosphorylated in cells overexpressing these cyclins, and this phosphorylation is essential for cyclin A- and cyclin E-mediated rescue of pRb-blocked cells. This suggests that G1 and S phase cyclins can act as regulators of pRb function in the cell cycle by promoting pRb phosphorylation.
Hinds
P W
PW
Whitehead Institute, Cambridge, Massachusetts 02142.
Mittnacht
S
S
Dulic
V
V
Arnold
A
A
Reed
S I
SI
Weinberg
R A
RA
D002467:Cell Nucleus; D016213:Cyclins / Q000378:metabolism / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016213:Cyclins; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D011494:Protein Kinases