Campbell S D, Sprenger F, Edgar B A, O'Farrell P H
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448, USA.
Mol Biol Cell. 1995 Oct;6(10):1333-47. doi: 10.1091/mbc.6.10.1333.
Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-inhibitory kinases that are required for preventing premature activation of the mitotic program. To identify Cdc2-inhibitory kinases in Drosophila, we screened for cDNA clones that rescue S. pombe wee1- mik1- mutants from lethal mitotic catastrophe. One of the genes identified in this screen, Drosophila wee1 (Dwee1), encodes a new Wee1 homologue. Dwee1 kinase is closely related to human and Xenopus Wee1 homologues, and can inhibit Cdc2 activity by phosphorylating a critical tyrosine residue. Dwee1 mRNA is maternally provided to embryos, and is zygotically expressed during the postblastoderm divisions of embryogenesis. Expression remains high in the proliferating cells of the central nervous system well after cells in the rest of the embryo have ceased dividing. The loss of zygotically expressed Dwee1 does not lead to mitotic catastrophe during postblastoderm cycles 14 to 16. This result may indicate that maternally provided Dwee1 is sufficient for regulating Cdc2 during embryogenesis, or it may reflect the presence of a redundant Cdc2 inhibitory kinase, as in fission yeast.
在所有已知的真核生物中，Cdc2激酶活性是触发进入有丝分裂所必需的。已经进化出了复杂的机制来调节Cdc2活性，以便在有丝分裂执行的准备工作完成时及时发生有丝分裂。在粟酒裂殖酵母中，Wee1和相关的Mik1激酶是Cdc2抑制激酶，它们是防止有丝分裂程序过早激活所必需的。为了在果蝇中鉴定Cdc2抑制激酶，我们筛选了能够拯救粟酒裂殖酵母wee1 - mik1 - 突变体免于致命有丝分裂灾难的cDNA克隆。在此筛选中鉴定出的一个基因，果蝇wee1（Dwee1），编码一种新的Wee1同源物。Dwee1激酶与人和非洲爪蟾的Wee1同源物密切相关，并且可以通过磷酸化一个关键的酪氨酸残基来抑制Cdc2活性。Dwee1 mRNA由母体提供给胚胎，并在胚胎发育的胚盘后分裂期间合子表达。在胚胎其余部分的细胞停止分裂后很长时间，中枢神经系统增殖细胞中的表达仍然很高。合子表达的Dwee1缺失在胚盘后第14至16个周期不会导致有丝分裂灾难。这一结果可能表明母体提供的Dwee1足以在胚胎发育过程中调节Cdc2，或者它可能反映了存在一种冗余的Cdc2抑制激酶，就像在裂殖酵母中一样。
