The Ski oncoprotein is upregulated and localized at the centrosomes and mitotic spindle during mitosis
The Ski oncoprotein is upregulated and localized at the centrosomes and mitotic spindle during mitosis
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DOI：
10.1038/sj.onc.1208631
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发表时间：
2005-06-01
期刊：
影响因子：
8
通讯作者：
Hayman, MJ
中科院分区：
文献类型：
--
作者：
Marcelain, K;Hayman, MJ
SKI是一种癌蛋白，它抑制转化生长因子-β和核受体信号转导。尽管有证据表明，Ski蛋白水平的增加与人类细胞中的肿瘤进展直接相关，但调节Ski表达的信号通路大多尚不清楚。在这里，我们发现Ski蛋白水平在整个细胞周期中都不同，在G0/G1时最低。这种Ski蛋白水平的降低是蛋白酶体降解的结果，如体内Ski的泛素化和蛋白酶体抑制剂的作用所表明的那样。相反，在经历有丝分裂的细胞中观察到Ski蛋白的上调。在这个阶段，我们还发现Ski是磷酸化的。体内外研究表明，Ski在有丝分裂过程中的磷酸化是由控制有丝分裂进程的主要激酶，即cdc2/cyClinB来实现的。有趣的是，在生化数据的支持下，免疫荧光实验表明，不仅Ski蛋白水平增加，而且在有丝分裂过程中，Ski戏剧性地重新分布到中心体和有丝分裂纺锤体。到目前为止，关于滑雪的研究主要集中在它作为转录调节因子的作用上。然而，Ski在有丝分裂过程中水平的升高和特异性的重新定位表明，Ski可能在细胞周期的这一特定阶段发挥着独特的作用。
Ski is an oncoprotein that represses transforming growth factor-beta and nuclear receptor signaling. Despite evidence that relates increased Ski protein levels directly with tumor progression in human cells, the signaling pathways that regulate Ski expression are mostly unidentified. Here we show that the Ski protein levels vary throughout the cell cycle, being lowest at G0/G1. This reduction in Ski protein levels results from proteosomal degradation as suggested by in vivo ubiquitination of Ski and the effects of proteosomal inhibitors. In contrast, an upregulation of the Ski protein was observed in cells going through mitosis. At this stage, we also found that Ski is phosphorylated. In vitro and in vivo data suggest that the phosphorylation of Ski in mitosis is carried out by the main kinase controlling the progression of mitosis, namely cdc2/cyclinB. Interestingly, immunofluorescence experiments, supported by biochemical data, show not only an increase in the Ski protein levels, but also a dramatic redistribution of Ski to the centrosomes and mitotic spindle throughout mitosis. Studies to date on Ski have focused on its role as a transcriptional regulator. However, Ski's increased level and specific relocalization during mitosis suggest that Ski might play a distinct role during this particular phase of the cell cycle.