Chen P L, Scully P, Shew J Y, Wang J Y, Lee W H
Department of Pathology M-012, University of California, San Diego, La Jolla 92093.
Cell. 1989 Sep 22;58(6):1193-8. doi: 10.1016/0092-8674(89)90517-5.
Introduction of an exogenous retinoblastoma (RB) gene in RB-deficient retinoblastoma or osteosarcoma cells has been shown to suppress their neoplastic phenotype. In experiments designed to explore the potential mechanism of RB tumor suppression, we report here that the phosphorylation state of RB protein is modulated during normal cellular events. In resting cells, RB protein is present in its least phosphorylated form; in rapidly proliferating cells, RB protein is highly phosphorylated. Maximal phosphorylation is associated with S phase of the cell cycle. Induction of differentiation in several human leukemia cell lines by treatment with phorbol ester or retinoic acid leads to dephosphorylation of RB. Time course studies indicate that RB dephosphorylation precedes the total arrest of cell growth during differentiation. These observations strongly suggest that the function of RB protein is modulated by a phosphorylation/dephosphorylation mechanism during cell proliferation and differentiation.
在缺乏视网膜母细胞瘤（RB）基因的视网膜母细胞瘤或骨肉瘤细胞中引入外源性RB基因已被证明可抑制其肿瘤表型。在旨在探索RB肿瘤抑制潜在机制的实验中，我们在此报告，RB蛋白的磷酸化状态在正常细胞事件中受到调节。在静止细胞中，RB蛋白以其磷酸化程度最低的形式存在；在快速增殖的细胞中，RB蛋白高度磷酸化。最大磷酸化与细胞周期的S期相关。用佛波酯或视黄酸处理诱导几种人白血病细胞系分化会导致RB去磷酸化。时间进程研究表明，RB去磷酸化在分化过程中细胞生长完全停滞之前发生。这些观察结果强烈表明，在细胞增殖和分化过程中，RB蛋白的功能通过磷酸化/去磷酸化机制受到调节。
