Requirements of Cyclin A for mitosis are independent of its subcellular localization
Requirements of Cyclin A for mitosis are independent of its subcellular localization
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DOI：
10.1016/j.cub.2004.06.024
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发表时间：
2004-06-22
期刊：
影响因子：
9.2
通讯作者：
Sprenger, F
中科院分区：
文献类型：
--
作者：
Dienemann, A;Sprenger, F
细胞周期蛋白A（Cyclin A，CycA）是果蝇有丝分裂中唯一必需的细胞周期蛋白[1]，在分裂间期位于细胞质中，在分裂前期积累于细胞核中[2]。我们发现，间期定位介导的瘦霉素B（LMB）敏感的核输出。这是与人CyclinB 1共有的特征，并且假定核积累是有丝分裂进入所必需的[3]。在这里，我们测试了CycA独特的有丝分裂功能是否需要核积累。我们将亚细胞定位信号与CycA融合，并测试其有丝分裂能力。令人惊讶的是，不需要核积累，甚至膜束缚形式的CycA也能够诱导有丝分裂。我们注意到，细胞周期蛋白B（CycB）蛋白在CycA突变体中过早消失，使人想起rca 1突变体。Rca 1是Fizzy-related-APC/C活性的抑制剂，在rca 1突变体中，有丝分裂细胞周期蛋白在第16个胚胎细胞周期的G2期降解[4]。Rca 1的过表达可以恢复CycA突变体的有丝分裂，表明CycA突变体的有丝分裂失败是由APC/C的过早激活引起的。因此，CycA的基本有丝分裂功能不是通过Cdk 1依赖性磷酸化激活许多有丝分裂底物。相反，需要CycA依赖性激酶活性来抑制有丝分裂的一种抑制剂Fzr蛋白。
Cyclin A (CycA), the only essential mitotic cyclin in Drosophila [1], is cytoplasmic during interphase and accumulates in the nucleus during prophase [2]. We show that interphase localization is mediated by Leptomycin B (LMB)-sensitive nuclear export. This is a feature shared with human CyclinB1, and it is assumed that nuclear accumulation is necessary for mitotic entry [3]. Here, we tested if the unique mitotic function of CycA requires nuclear accumulation. We fused subcellular localization signals to CycA and tested their mitotic capability. Surprisingly, nuclear accumulation was not required, and even a membrane-tethered form of CycA was able to induce mitosis. We noted that Cyclin B (CycB) protein disappears prematurely in CycA mutants, reminiscent of rca1 mutants. Rca1 is an inhibitor of Fizzy-related-APC/C activity, and in rca1 mutants, mitotic cyclins are degraded in G2 of the 16(th) embryonic cell cycle [4]. Overexpression of Rca1 can restore mitosis in CycA mutants, indicating that the mitotic failure of CycA mutants is caused by premature activation of the APC/C. The essential mitotic function of CycA is therefore not the activation of numerous mitotic substrates by Cdk1-dependent phosphorylation. Rather, CycA-dependent kinase activity is required to inhibit one inhibitor of mitosis, the Fzr protein.