PMID- 1388095 OWN - NLM STAT- MEDLINE DCOM- 19921019 LR - 20220321 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 70 IP - 6 DP - 1992 Sep 18 TI - Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. PG - 993-1006 AB - 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. FAU - Hinds, P W AU - Hinds PW AD - Whitehead Institute, Cambridge, Massachusetts 02142. FAU - Mittnacht, S AU - Mittnacht S FAU - Dulic, V AU - Dulic V FAU - Arnold, A AU - Arnold A FAU - Reed, S I AU - Reed SI FAU - Weinberg, R A AU - Weinberg RA LA - eng GR - CA55909/CA/NCI NIH HHS/United States GR - GM38328/GM/NIGMS NIH HHS/United States GR - GM46006/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Cyclins) RN - 0 (Recombinant Proteins) RN - 0 (Retinoblastoma Protein) RN - EC 2.7.- (Protein Kinases) SB - IM MH - Cell Nucleus MH - Cyclins/metabolism/*physiology MH - G1 Phase/physiology MH - Gene Expression MH - Genetic Vectors MH - Humans MH - Mutation MH - Phenotype MH - Phosphorylation MH - Protein Kinases MH - Recombinant Proteins MH - Retinoblastoma Protein/*physiology MH - Transfection MH - Tumor Cells, Cultured EDAT- 1992/09/18 00:00 MHDA- 1992/09/18 00:01 CRDT- 1992/09/18 00:00 PHST- 1992/09/18 00:00 [pubmed] PHST- 1992/09/18 00:01 [medline] PHST- 1992/09/18 00:00 [entrez] AID - 0092-8674(92)90249-C [pii] AID - 10.1016/0092-8674(92)90249-c [doi] PST - ppublish SO - Cell. 1992 Sep 18;70(6):993-1006. doi: 10.1016/0092-8674(92)90249-c.