Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin
Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin
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DOI：
10.1038/nature06388
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发表时间：
2007-12-20
期刊：
影响因子：
64.8
通讯作者：
Meyer, Hemmo H.
中科院分区：
文献类型：
--
作者：
Ramadan, Kristijan;Bruderer, Roland;Meyer, Hemmo H.
在后生动物细胞分裂期间，细胞核分解以允许染色体分离，然后在每个子细胞中重组。细胞核的重组涉及染色质解浓缩和染色质周围双膜核膜的组装；然而，人们对这一过程的调控仍知之甚少(1,2)。在体外，细胞核形成需要 p97（参考文献 3），这是一种参与膜融合和泛素依赖性过程的六聚体 ATP 酶 (4,5)。然而，p97 在细胞核形成中的作用和相关性仍然存在争议。在这里，我们发现 p97 通过灭活染色质相关激酶 Aurora B 来刺激细胞核重构。在有丝分裂期间，Aurora B 通过阻止染色体解浓缩和核膜形成来抑制细胞核重构。在有丝分裂退出期间，p97 在泛素化后与 Aurora B 结合，并将其从染色质中提取出来。这导致染色质上的 Aurora B 失活，从而允许染色质解凝和核膜形成。这些数据揭示了有丝分裂后调节细胞核重组的重要途径，并将泛素依赖性蛋白质提取定义为细胞核形成过程中 Cdc48/p97 活性的常见机制。
During division of metazoan cells, the nucleus disassembles to allow chromosome segregation, and then reforms in each daughter cell. Reformation of the nucleus involves chromatin decondensation and assembly of the double- membrane nuclear envelope around the chromatin; however, regulation of the process is still poorly understood(1,2). In vitro, nucleus formation requires p97 ( ref. 3), a hexameric ATPase implicated in membrane fusion and ubiquitin- dependent processes(4,5). However, the role and relevance of p97 in nucleus formation have remained controversial. Here we show that p97 stimulates nucleus reformation by inactivating the chromatin- associated kinase Aurora B. During mitosis, Aurora B inhibits nucleus reformation by preventing chromosome decondensation and formation of the nuclear envelope membrane. During exit from mitosis, p97 binds to Aurora B after its ubiquitylation and extracts it from chromatin. This leads to inactivation of Aurora B on chromatin, thus allowing chromatin decondensation and nuclear envelope formation. These data reveal an essential pathway that regulates reformation of the nucleus after mitosis and defines ubiquitin- dependent protein extraction as a common mechanism of Cdc48/p97 activity also during nucleus formation.