Hinds, PW and Mittnacht, S and Dulic, V and Arnold, A and Reed, SI and Weinberg, RA (1992) Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell , 70 (6) 993 - 1006.
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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.
|Title:||Regulation of retinoblastoma protein functions by ectopic expression of human cyclins.|
|Keywords:||Cell Nucleus, Cyclins, G1 Phase, Gene Expression, Genetic Vectors, Humans, Mutation, Phenotype, Phosphorylation, Protein Kinases, Recombinant Proteins, Retinoblastoma Protein, Transfection, Tumor Cells, Cultured|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Cancer Biology|
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