REGULATION OF RETINOBLASTOMA PROTEIN FUNCTIONS BY ECTOPIC EXPRESSION OF HUMAN CYCLINS
REGULATION OF RETINOBLASTOMA PROTEIN FUNCTIONS BY ECTOPIC EXPRESSION OF HUMAN CYCLINS
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DOI：
10.1016/0092-8674(92)90249-c
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发表时间：
1992-09-18
期刊：
影响因子：
64.5
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
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作者：
HINDS, PW;MITTNACHT, S;WEINBERG, RA
视网膜母细胞瘤易感基因（RB）产物视网膜母细胞瘤蛋白（pRb）在细胞增殖中起调节作用。将RB基因导入缺乏功能性pRb的SAOS-2骨肉瘤细胞，可阻止细胞周期的进展。这种生长抑制功能可以通过pRb的磷酸化来调节，这是通过细胞周期调节激酶发生的。我们发现组成型表达的细胞周期蛋白A和E可以克服prb介导的增殖抑制。在过度表达这些细胞周期蛋白的细胞中，pRb会过度磷酸化，这种磷酸化对于细胞周期蛋白A和细胞周期蛋白e介导的pRb阻断细胞的拯救至关重要。这表明G1期和S期细胞周期蛋白可以通过促进pRb磷酸化在细胞周期中发挥pRb功能的调节作用。
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.