GROWTH-INHIBITION BY TGF-BETA LINKED TO SUPPRESSION OF RETINOBLASTOMA PROTEIN-PHOSPHORYLATION
GROWTH-INHIBITION BY TGF-BETA LINKED TO SUPPRESSION OF RETINOBLASTOMA PROTEIN-PHOSPHORYLATION
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DOI：
10.1016/0092-8674(90)90251-9
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发表时间：
1990-07-13
期刊：
影响因子：
64.5
通讯作者：
MASSAGUE, J
中科院分区：
文献类型：
--
作者：
LAIHO, M;DECAPRIO, JA;MASSAGUE, J
视网膜母细胞瘤基因产物RB的生长抑制功能已被归因于在细胞周期的G1期期间普遍存在的磷酸化不足的RB形式。我们表明，在G1中期至晚期向Mv 1 Lu肺上皮细胞添加旁分泌生长抑制剂转化生长因子β 1（TGF-β 1）阻止了为该细胞周期阶段安排的RB磷酸化，并在G1晚期阻滞细胞。SV 40 T抗原（一种结合磷酸化不足的RB的转化蛋白）的表达不阻断TGF-β 1对RB磷酸化的作用，但大大降低了对TGF-β 1的生长抑制反应。TGF-β 1和RB似乎在共同的生长抑制途径中起作用，其中TGF-β 1起到将RB保持在磷酸化不足的生长抑制状态的作用。
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.