Krien M J, Bugg S J, Palatsides M, Asouline G, Morimyo M, O'Connell M J
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, Australia.
J Cell Sci. 1998 Apr;111 ( Pt 7):967-76. doi: 10.1242/jcs.111.7.967.
Entry into mitosis requires p34(cdc2), which activates downstream mitotic events through phosphorylation of key target proteins. In Aspergillus nidulans, the NIMA protein kinase has been identified as a potential downstream target and plays a role in regulating chromatin condensation at mitosis. nimA- mutants arrest in a state that physically resembles interphase even though p34(cdc2) is fully active. Despite evidence for the existence of NIMA-like activities in a variety of cell types, the only bona fide NIMA homologue that has been identified is the nim-1 gene of Neurospora crassa. We report here the isolation of a fission yeast NIMA homologue, and have designated this gene fin1 and the 83 kDa predicted protein p83(fin1). Overexpression of fin1 promotes premature chromatin condensation from any point in the cell cycle independently of p34(cdc2) function. Like NIMA, p83(fin1) levels fluctuate through the cell cycle, peaking in mitosis and levels are greatly elevated by removal of C-terminal PEST sequences. Deletion of fin1 results in viable but elongated cells, indicative of a cell cycle delay. Genetic analysis has placed this delay in G2 but, unlike in nimA mutants of Aspergillus, p34(cdc2) activation appears to be delayed. Interaction of fin1 mutants with other strains defective in chromatin organisation also support the hypothesis of p83(fin1) playing a role in this process at the onset of mitosis. These data indicate that NIMA-related kinases may be a general feature of the cell cycle and chromatin organisation at mitosis.
进入有丝分裂需要p34(cdc2)，它通过磷酸化关键靶蛋白来激活下游的有丝分裂事件。在构巢曲霉中，NIMA蛋白激酶已被确定为一个潜在的下游靶标，并在有丝分裂过程中调节染色质凝聚方面发挥作用。nimA - 突变体停滞在一种形态上类似于间期的状态，尽管p34(cdc2)完全活跃。尽管有证据表明在多种细胞类型中存在NIMA样活性，但唯一已确定的真正NIMA同源物是粗糙脉孢菌的nim - 1基因。我们在此报告了一种裂殖酵母NIMA同源物的分离，并将该基因命名为fin1，预测的83 kDa蛋白命名为p83(fin1)。fin1的过表达能在细胞周期的任何时间点促进染色质提前凝聚，且与p34(cdc2)的功能无关。与NIMA一样，p83(fin1)的水平在细胞周期中波动，在有丝分裂时达到峰值，并且通过去除C末端的PEST序列，其水平会大幅升高。fin1的缺失导致细胞存活但变长，这表明细胞周期延迟。遗传分析表明这种延迟发生在G2期，但与构巢曲霉的nimA突变体不同，p34(cdc2)的激活似乎也被延迟了。fin1突变体与其他染色质组织缺陷菌株的相互作用也支持了p83(fin1)在有丝分裂开始时参与这一过程的假说。这些数据表明，NIMA相关激酶可能是细胞周期和有丝分裂时染色质组织的一个普遍特征。
