Drosophila Wee1 kinase regulates Cdk1 and mitotic entry during embryogenesis
Drosophila Wee1 kinase regulates Cdk1 and mitotic entry during embryogenesis
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DOI：
10.1016/j.cub.2004.11.050
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发表时间：
2004-12-14
期刊：
影响因子：
9.2
通讯作者：
Su, TT
中科院分区：
文献类型：
--
作者：
Stumpff, J;Duncan, T;Su, TT
细胞周期蛋白依赖性蛋白激酶(CDK)是细胞分裂周期的中央调节因子。CDKs的抑制剂确保了细胞周期事件的适当协调，并有助于调节组织和器官中的细胞增殖。Wee1同系物使保守的酪氨酸磷酸化，从而抑制有丝分裂的细胞周期蛋白依赖性激酶CDK1[1]。在分裂或萌芽酵母中Wee1功能的丧失会导致过早进入有丝分裂[2，3]。然而，后生动物Wee1同系物对定时有丝分裂的重要性仅在非洲爪哇卵提取液中和通过异位CDK1激活[4，5]被证明。在这里，我们报道了果蝇Wee1(DWee1)通过酪氨酸15的磷酸化和在缺乏间隙相的合体胚皮层核周期中的有丝分裂进入来调节CDK1。母体Dwe1的丢失会导致过早进入有丝分裂，有丝分裂纺锤体缺陷，染色体凝集问题，以及依赖Chk2的后续发育障碍，进而导致胚胎死亡。这些发现修正了以前关于合体胚胎细胞周期调控的模型[6]，并证明了Wee1激酶可以在后生动物发育过程中调节体内有丝分裂的进入，即使在缺乏G2期的周期中也是如此。
Cyclin-dependent kinases (Cdks) are the central regulators of the cell division cycle. Inhibitors of Cdks ensure proper coordination of cell cycle events and help regulate cell proliferation in the context of tissues and organs. Wee1 homologs phosphorylate a conserved tyrosine to inhibit the mitotic cyclin-dependent kinase Cdk1 [1]. Loss of Wee1 function in fission or budding yeast causes premature entry into mitosis [2, 3]. The importance of metazoan Wee1 homologs for timing mitosis, however, has been demonstrated only in Xenopus egg extracts and via ectopic Cdk1 activation [4, 5]. Here, we report that Drosophila Wee1 (dWee1) regulates Cdk1 via phosphorylation of tyrosine 15 and times mitotic entry during the cortical nuclear cycles of syncytial blastoderm embryos, which lack gap phases. Loss of maternal dwee1 leads to premature entry into mitosis, mitotic spindle defects, chromosome condensation problems, and a Chk2-dependent block of subsequent development, and then embryonic lethality. These findings modify previous models about cell cycle regulation in syncytial embryos [6] and demonstrate that Wee1 kinases can regulate mitotic entry in vivo during metazoan development even in cycles that lack a G2 phase.