Siah1/SIP 调控代谢应激下 p27(kip1) 的稳定性和细胞迁移。
Siah1/SIP regulates p27(kip1) stability and cell migration under metabolic stress.
机构信息
Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
出版信息
Cell Cycle. 2011 Aug 1;10(15):2592-602. doi: 10.4161/cc.10.15.16912.
Abstract
p27(kip1) has been implicated in cell cycle regulation, functioning as an inhibitor of cyclin-dependent kinase activity. In addition, p27 was also shown to affect cell migration, with accumulation of cytoplasmic p27 associated with tumor invasiveness. However, the mechanism underlying p27 regulation as a cytoplasmic protein is poorly understood. Here we show that glucose starvation induces proteasome-dependent degradation of cytoplasmic p27, accompanied by a decrease in cell motility. We also show that the glucose limitation-induced p27 degradation is regulated through an ubiquitin E3 ligase complex involving Siah1 and SIP/CacyBP. SIP (-/-) embryonic fibroblasts have increased levels of cytosolic p27 and exhibit increased cell motility compared to wild-type cells. These observations suggest that the Siah1/SIP E3 ligase complex regulates cell motility through degradation of p27.
摘要
p27(kip1) 参与细胞周期调控，作为细胞周期蛋白依赖性激酶活性的抑制剂。此外，p27 还被证明会影响细胞迁移，细胞质中 p27 的积累与肿瘤侵袭性有关。然而，作为细胞质蛋白的 p27 调节的机制还知之甚少。在这里，我们表明葡萄糖饥饿诱导细胞质 p27 的蛋白酶体依赖性降解，同时细胞迁移能力下降。我们还表明，葡萄糖限制诱导的 p27 降解是通过涉及 Siah1 和 SIP/CacyBP 的泛素 E3 连接酶复合物调节的。SIP(-/-) 胚胎成纤维细胞中细胞质 p27 的水平升高，与野生型细胞相比，细胞迁移能力增强。这些观察结果表明，Siah1/SIP E3 连接酶复合物通过降解 p27 来调节细胞迁移。
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