Ramadan Kristijan, Bruderer Roland, Spiga Fabio M, Popp Oliver, Baur Tina, Gotta Monica, Meyer Hemmo H
Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
Nature. 2007 Dec 20;450(7173):1258-62. doi: 10.1038/nature06388.
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. In vitro, nucleus formation requires p97 (ref. 3), a hexameric ATPase implicated in membrane fusion and ubiquitin-dependent processes. 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.
在后生动物细胞分裂过程中,细胞核解体以允许染色体分离,然后在每个子细胞中重新形成。细胞核的重新形成涉及染色质解聚以及围绕染色质组装双膜核膜;然而,该过程的调控仍知之甚少。在体外,细胞核形成需要p97(参考文献3),一种参与膜融合和泛素依赖性过程的六聚体ATP酶。然而,p97在细胞核形成中的作用和相关性仍存在争议。在这里,我们表明p97通过使与染色质相关的激酶Aurora B失活来刺激细胞核重新形成。在有丝分裂期间,Aurora B通过阻止染色体解聚和核膜形成来抑制细胞核重新形成。在有丝分裂退出期间,p97在Aurora B泛素化后与其结合并将其从染色质中提取出来。这导致Aurora B在染色质上失活,从而允许染色质解聚和核膜形成。这些数据揭示了一条调节有丝分裂后细胞核重新形成的重要途径,并将泛素依赖性蛋白提取定义为细胞核形成过程中Cdc48/p97活性的一种常见机制。