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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin
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Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin

机译：Aurora B是有丝分裂染色质诱导的Op18 / Stathmin磷酸化所必需的

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摘要

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.
机译：Oncoprotein 18 Stathmin（Op18）是一种微管不稳定蛋白，可响应多种信号而被磷酸化抑制。在有丝分裂期间，cdc2对Op18的磷酸化是必需的，但不足以抑制Op18。另外需要有丝分裂染色体的存在，并且涉及非洲爪蟾Op18中Ser-16（和/或人中Ser-63）的磷酸化。鉴于Ser-16是一个极好的Aurora A（Aur-A）激酶共有磷酸化位点，并且Aurora激酶抑制剂ZM447439（ZM）阻断了Aur-A的激活环中的磷酸化，我们询问Aur-A还是Aurora B（ Aur-B）可能会调节Op18。我们发现ZM阻止有丝分裂染色质诱导非洲爪蟾卵提取物中的Op18过度磷酸化的能力。耗尽Aur-B（而不是Aur-A）会阻止Op18的过度磷酸化，并且在不存在Aur-B的情况下组装的染色质不能诱导过度磷酸化。这些结果表明，Aur-B集中在中期染色体的着丝粒上，在纺锤体组装过程中有助于Op18的局部调控。

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