Dawson I A, Roth S, Artavanis-Tsakonas S
Department of Cell Biology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-0812, USA.
J Cell Biol. 1995 May;129(3):725-37. doi: 10.1083/jcb.129.3.725.
The Drosophila cell cycle gene fizzy (fzy) is required for normal execution of the metaphase-anaphase transition. We have cloned fzy, and confirmed this by P-element mediated germline transformation rescue. Sequence analysis predicts that fzy encodes a protein of 526 amino acids, the carboxy half of which has significant homology to the Saccharomyces cerevisiae cell cycle gene CDC20. A monoclonal antibody against fzy detects a single protein of the expected size, 59 kD, in embryonic extracts. In early embryos fzy is expressed in all proliferating tissues; in late embryos fzy expression declines in a tissue-specific manner correlated with cessation of cell division. During interphase fzy protein is present in the cytoplasm; while in mitosis fzy becomes ubiquitously distributed throughout the cell except for the area occupied by the chromosomes. The metaphase arrest phenotype caused by fzy mutations is associated with failure to degrade both mitotic cyclins A and B, and an enrichment of spindle microtubules at the expense of astral microtubules. Our data suggest that fzy function is required for normal cell cycle-regulated proteolysis that is necessary for successful progress through mitosis.
果蝇细胞周期基因fizzy(fzy)对于中期-后期转换的正常执行是必需的。我们已经克隆了fzy,并通过P因子介导的种系转化拯救证实了这一点。序列分析预测fzy编码一个526个氨基酸的蛋白质,其羧基末端与酿酒酵母细胞周期基因CDC20具有显著同源性。一种针对fzy的单克隆抗体在胚胎提取物中检测到一个预期大小为59 kD的单一蛋白质。在早期胚胎中,fzy在所有增殖组织中表达;在晚期胚胎中,fzy表达以与细胞分裂停止相关的组织特异性方式下降。在间期,fzy蛋白存在于细胞质中;而在有丝分裂期间,fzy除了染色体占据的区域外,在整个细胞中普遍分布。由fzy突变引起的中期停滞表型与有丝分裂周期蛋白A和B未能降解以及纺锤体微管以星体微管为代价的富集有关。我们的数据表明,fzy功能对于正常的细胞周期调节蛋白水解是必需的,而这对于有丝分裂的成功进行是必要的。