Laiho M, DeCaprio J A, Ludlow J W, Livingston D M, Massagué J
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cell. 1990 Jul 13;62(1):175-85. doi: 10.1016/0092-8674(90)90251-9.
The growth-suppressive function of the retinoblastoma gene product, RB, has been ascribed to the underphosphorylated RB form that prevails during G1 phase in the cell cycle. We show that addition of the paracrine growth inhibitor transforming growth factor beta 1 (TGF-beta 1) to Mv1Lu lung epithelial cells in mid to late G1 prevents phosphorylation of RB scheduled for this cell cycle stage and arrests cells in late G1. Expression of SV40 T antigen, a transforming protein that binds underphosphorylated RB, does not block the effect of TGF-beta 1 on RB phosphorylation but greatly reduces the growth-inhibitory response to TGF-beta 1. TGF-beta 1 and RB appear to function in a common growth-inhibitory pathway in which TGF-beta 1 acts to retain RB in the underphosphorylated, growth-suppressive state.
视网膜母细胞瘤基因产物RB的生长抑制功能，被归因于在细胞周期G1期占主导的低磷酸化RB形式。我们发现，在G1期中期至后期向Mv1Lu肺上皮细胞添加旁分泌生长抑制剂转化生长因子β1（TGF-β1），可阻止该细胞周期阶段预定的RB磷酸化，并使细胞停滞在G1期后期。SV40 T抗原是一种与低磷酸化RB结合的转化蛋白，其表达并不阻断TGF-β1对RB磷酸化的作用，但大大降低了对TGF-β1的生长抑制反应。TGF-β1和RB似乎在一条共同的生长抑制途径中发挥作用，其中TGF-β1的作用是使RB保持在低磷酸化的生长抑制状态。
