Diamantina Institute, Princess Alexandra Hospital, The University of Queensland, Brisbane, Australia.
Biol Cell. 2011 Feb;103(2):55-68. doi: 10.1042/BC20100111.
CDC25 (cell division cycle 25) phosphatases function as activators of CDK (cyclin-dependent kinase)-cyclin complexes to regulate progression through the CDC. We have recently identified a pool of CDC25B at the centrosome of interphase cells that plays a role in regulating centrosome numbers.
In the present study, we demonstrate that CDC25B forms a close association with Ctn (centrin) proteins at the centrosome. This interaction involves both N- and C-terminal regions of CDC25B and requires CDC25B binding to its CDK-cyclin substrates. However, the interaction is not dependent on the enzyme activity of CDC25B. Although CDC25B appears to bind indirectly to Ctn2, this association is pertinent to CDC25B localization at the centrosome. We further demonstrate that CDC25B plays a role in maintaining the overall integrity of the centrosome, by regulating the centrosome levels of multiple centrosome proteins, including that of Ctn2.
Our results therefore suggest that CDC25B associates with a Ctn2-containing multiprotein complex in the cytoplasm, which targets it to the centrosome, where it plays a role in maintaining the centrosome levels of Ctn2 and a number of other centrosome components.
CDC25(细胞分裂周期 25)磷酸酶作为 CDK(细胞周期蛋白依赖性激酶)-细胞周期蛋白复合物的激活剂发挥作用,以调节细胞周期的进展。我们最近在间期细胞的中心体中发现了一组 CDC25B,它在调节中心体数量方面发挥作用。
在本研究中,我们证明 CDC25B 在中心体与 Ctn(中心粒蛋白)蛋白形成紧密的关联。这种相互作用涉及 CDC25B 的 N 端和 C 端区域,并且需要 CDC25B 与其 CDK-细胞周期蛋白底物结合。然而,这种相互作用不依赖于 CDC25B 的酶活性。尽管 CDC25B 似乎与 Ctn2 间接结合,但这种关联与 CDC25B 在中心体的定位有关。我们进一步证明,CDC25B 通过调节多种中心体蛋白的中心体水平,包括 Ctn2,在维持中心体的整体完整性方面发挥作用。
因此,我们的结果表明,CDC25B 在细胞质中与包含 Ctn2 的多蛋白复合物相关联,该复合物将其靶向中心体,在那里它在维持 Ctn2 和许多其他中心体成分的中心体水平方面发挥作用。