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首页> 外文期刊>Cell cycle >Glycogen synthase kinase-3 phosphorylates and regulates the stability of p27kip1 protein.
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Glycogen synthase kinase-3 phosphorylates and regulates the stability of p27kip1 protein.

机译：糖原合酶激酶3磷酸化并调节p27kip1蛋白的稳定性。

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摘要

p27Kip1 is a critical regulator of the eukaryotic cell cycle. It acts as a check point protein and regulates cell cycle progression at the G1 and G1/S phase as well as predominantly blocks cell cycle progression in the absence of growth factors. Intracellular turnover of p27 is tightly regulated at the level of translation as well as by posttranslational modification. The mechanism by which p27 protein is rapidly degraded during the G1 and G1/S phase transition is well characterized. However, the process by which p27 remains extremely stable in the absence of growth factors remains unknown. Here, we report that GSK-3 dependent phosphorylation of p27 protein is essential for its enhanced stability. p27 protein harbours 2 functional GSK-3 phosphorylation sites at the C- terminus, which was found to be effectively phosphorylated by the cognate enzyme both in vitro and in vivo. Combined with earlier observation which shows that it phosphorylates and triggers cyclin D degradation; GSK-3 now appears to be a central mediator of the cell-cycle regulatory network, where it acts as a two-way switch, phosphorylating and targeting pro-proliferative factors for degradation on one hand and simultaneously phosphorylating and stabilizing an anti-proliferative factor on the other hand. This dual mode of activity may doubly ensure that cell cycle progression is aptly prohibited under conditions of limited growth factor availability.
机译：p27Kip1是真核细胞周期的关键调控因子。它充当检查点蛋白并调节G1和G1 / S期的细胞周期进程，并在不存在生长因子的情况下主要阻断细胞周期进程。 p27的细胞内转换在翻译水平以及翻译后修饰中受到严格调节。 p27蛋白在G1和G1 / S相变过程中快速降解的机制已得到很好的表征。然而，在没有生长因子的情况下，p27保持极其稳定的过程仍然未知。在这里，我们报告p27蛋白的GSK-3依赖磷酸化对其增强的稳定性至关重要。 p27蛋白在C末端带有2个功能性GSK-3磷酸化位点，发现该蛋白在体外和体内均可被同源酶有效地磷酸化。与先前的观察结果相结合，该结果表明其磷酸化并触发细胞周期蛋白D降解;现在，GSK-3似乎是细胞周期调控网络的中央介体，在其中它起双向作用，一方面磷酸化和靶向促进增殖因子降解，同时又使抗增殖因子磷酸化并稳定另一方面。这种双重活动模式可以双重确保在生长因子可用性有限的条件下适当禁止细胞周期进程。

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