Biosignal Research Center, Kobe University, Kobe, Japan.
Cell Cycle. 2013 Aug 15;12(16):2617-24. doi: 10.4161/cc.25623. Epub 2013 Jul 11.
Cyclins control cell cycle progression by regulating the activity of cyclin-dependent kinases (Cdks). Cyclin I is a member of the cyclin family because of the presence of a cyclin box motif. It has been suggested that Cyclin I is involved in various biological processes, such as cell survival, angiogenesis, and cell differentiation. However, whether or not Cyclin I has a role in regulating the cell cycle similarly to other cyclins has yet to be clarified. Therefore, we investigated the role for Cyclin I in cell cycle progression. We showed that the protein level of Cyclin I oscillated during the cell cycle, and that Cyclin I was subjected to ubiquitination and degradation in cells. The interaction between Cyclin I and Cdk5 was detected in cells overexpressed with both proteins. Furthermore, depletion of Cyclin I by siRNAs prevented cell proliferation, suggesting the positive role of Cyclin I for the cell cycle progression. In addition, flow cytometric analysis revealed that cells depleted of Cyclin I were accumulated at G₂/M phases. By using HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, we further confirmed that knockdown of Cyclin I induced cell cycle arrest at S/G₂/M phases. These results strongly suggest that Cyclin I has the role in the regulation of cell cycle progression.
细胞周期蛋白通过调节细胞周期蛋白依赖性激酶(Cdks)的活性来控制细胞周期进程。Cyclin I 因其存在 cyclin 盒基序而被认为是 cyclin 家族的一员。已经表明 Cyclin I 参与了各种生物学过程,如细胞存活、血管生成和细胞分化。然而,Cyclin I 是否像其他细胞周期蛋白一样在调节细胞周期中发挥作用仍未得到澄清。因此,我们研究了 Cyclin I 在细胞周期进程中的作用。我们表明,Cyclin I 的蛋白水平在细胞周期中波动,并且 Cyclin I 在细胞中受到泛素化和降解。在同时过表达两种蛋白质的细胞中检测到 Cyclin I 与 Cdk5 的相互作用。此外,通过 siRNA 耗尽 Cyclin I 可阻止细胞增殖,表明 Cyclin I 对细胞周期进程具有正向作用。此外,流式细胞术分析显示,耗尽 Cyclin I 的细胞在 G₂/M 期积累。通过使用 HeLa.S-Fucci(基于荧光泛素化的细胞周期指示剂)细胞,我们进一步证实了 Cyclin I 的敲低诱导 S/G₂/M 期的细胞周期停滞。这些结果强烈表明 Cyclin I 在调节细胞周期进程中具有作用。