On the regulation and function of human polo-like kinase 1 (PLK1): Effects of overexpression on cell cycle progression
On the regulation and function of human polo-like kinase 1 (PLK1): Effects of overexpression on cell cycle progression
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DOI：
10.1006/bbrc.1997.7378
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发表时间：
1997-10-20
影响因子：
3.1
通讯作者：
Nigg, EA
中科院分区：
文献类型：
--
作者：
Mundt, KE;Golsteyn, RM;Nigg, EA
人蛋白激酶Plk 1是polo样激酶家族的成员，已知在有丝分裂中发挥作用。在这里，我们表明，Plk 1的相对比活性增加有丝分裂，Plk 1在有丝分裂过程中特异性磷酸化，磷酸酶处理有丝分裂Plk 1活性降低到间期水平。为了确定参与Plk 1活性调节的结构域，构建Plk 1的缺失突变体并检测其活性。Plk 1的极端C-末端的缺失大大增加了激酶活性，表明C-末端含有抑制结构域。最后，野生型和突变体Plk 1蛋白的过度生产的后果进行了分析，使用瞬时转染试验。过表达Plk 1蛋白的细胞能够进入有丝分裂，并建立一个明显正常的双极纺锤体。相反，通过有丝分裂的进展是短暂的延迟，胞质分裂似乎受到干扰，反映了一个显着增加的大细胞与多个，往往破碎的核。这些结果是有关最近提出的Plks在进入和退出有丝分裂的作用。(C)北京：科学出版社.
The human protein kinase Plk1, a member of the polo-like kinase family, is known to function at mitosis. Here we show that the relative specific activity of Plk1 increases in mitosis, that Plk1 is specifically phosphorylated during mitosis, and that phosphatase treatment reduces mitotic Plk1 activity to interphase levels. To identify domains involved in the regulation of Plk1 activity, deletion mutants of Plk1 were constructed and their activities examined. Deletion of the extreme C-terminus of Plk1 substantially increased kinase activity, indicating that the C-terminus harbors an inhibitory domain. Finally, the consequences of over-production of wild-type and mutant Plk1 protein were analyzed, using transient transfection assays. Cells overexpressing Plk1 protein were able to enter mitosis and establish an apparently normal bipolar spindle. In contrast, progression through mitosis was transiently delayed, and cytokinesis appeared to be disturbed, as reflected by a significant increase in large cells with multiple, often fragmented nuclei. These results are relevant to recently proposed roles for Plks during both entry into and exit from mitosis. (C) 1997 Academic Press.