Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin
Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin
复制标题
DOI：
10.1073/pnas.0600702103
复制
发表时间：
2006-03-21
影响因子：
11.1
通讯作者：
Ruderman, JV
中科院分区：
文献类型：
--
作者：
Gadea, BB;Ruderman, JV
癌蛋白18/stathmin(OP18)是一种微管失稳蛋白，可在多种信号作用下被磷酸化抑制。在有丝分裂过程中，CDC2对OP18的磷酸化是必要的，但不足以抑制OP18。有丝分裂染色体的存在是额外需要的，它涉及非洲爪哇OP18(和/或人类的Ser-63)中Ser-16的磷酸化。鉴于Ser-16是一个很好的Aurora A(Aur-A)激酶共同磷酸化位点，而Aurora激酶抑制剂ZM447439(ZM)阻断了Aur-A激活环中的磷酸化，我们询问Aur-A或Aurora B(Aur-B)是否可能调节OP18。我们发现ZM阻断了有丝分裂染色质诱导非洲爪哇卵提取物OP18过度磷酸化的能力。Aur-B的耗尽，而不是Aur-A的耗尽，阻止了OP18的过度磷酸化，在没有Aur-B的情况下组装的染色质未能诱导过度磷酸化。这些结果表明，集中在中期染色体着丝粒的Aur-B参与了纺锤体组装过程中OP18的局部调控。
Oncoprotein 18/Stathmin (Op18) is a microtubule-destabilizing protein that is inhibited by phosphorylation in response to many types of signals. During mitosis, phosphorylation of Op18 by cdc2 is necessary but not sufficient for Op18 inhibition. The presence of mitotic chromosomes is additionally required and involves phosphorylation of Ser-16 in Xenopus Op18 (and/or Ser-63 in human). Given that Ser-16 is an excellent Aurora A (Aur-A) kinase consensus phosphorylation site and the Aurora kinase inhibitor ZM447439 (ZM) blocks phosphorylation in the activation loop of Aur-A, we asked whether either Aur-A or Aurora B (Aur-B) might regulate Op18. We find that ZM blocks the ability of mitotic chromatin to induce Op18 hyperphosphorylation in Xenopus egg extracts. Depletion of Aur-B, but not Aur-A, blocks hyperphosphorylation of Op18, and chromatin assembled in the absence of Aur-B fails to induce hyperphosphorylation. These results suggest that Aur-B, which concentrates at centromeres of metaphase chromosomes, contributes to localized regulation of Op18 during the process of spindle assembly.