Caenorhabditis elegans Geminin Homologue Participates in Cell Cycle Regulation and Germ Line Development*
Caenorhabditis elegans Geminin Homologue Participates in Cell Cycle Regulation and Germ Line Development*
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DOI：
10.1074/jbc.c500070200
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发表时间：
2005-05
影响因子：
4.8
通讯作者：
K. Yanagi;T. Mizuno;Takashi Tsuyama;S. Tada;Yumi Iida;A. Sugimoto;T. Eki;T. Enomoto;F. Hanaoka
中科院分区：
文献类型：
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作者：
K. Yanagi;T. Mizuno;Takashi Tsuyama;S. Tada;Yumi Iida;A. Sugimoto;T. Eki;T. Enomoto;F. Hanaoka
cdt 1是复制前复合体组装的重要组成部分。cdt 1的活性被双生蛋白抑制，双生蛋白也参与许多真核生物的神经发育和胚胎分化。虽然Cdt 1同源物已经在从酵母到人类的生物体中被鉴定，但在秀丽隐杆线虫和真菌中还没有描述双生蛋白同源物。在这里，我们确定了C。线虫双生蛋白GMN-1。生化分析表明，GMN-1与C.线虫CDT-1、Hox蛋白NOB-1和Six蛋白CEH-32。GMN-1不仅抑制小鼠Cdt 1和Mcm 6之间的相互作用，而且抑制爪蟾卵提取物中的许可活性。RNA干扰介导的GMN-1减少与生殖核增大伴异常核仁形态、严重受损的配子发生和肠细胞中的染色体桥接有关。我们的结论是，Cdt 1-双生蛋白系统在整个后生动物中是保守的，并且双生蛋白在这些分类群中已经进化，通过直接与Cdt 1和同源盒蛋白相互作用来调节增殖和分化。
Cdt1 is an essential component for the assembly of a pre-replicative complex. Cdt1 activity is inhibited by geminin, which also participates in neural development and embryonic differentiation in many eukaryotes. Although Cdt1 homologues have been identified in organisms ranging from yeast to human, geminin homologues had not been described for Caenorhabditis elegans and fungi. Here, we identify the C. elegans geminin, GMN-1. Biochemical analysis reveals that GMN-1 associates with C. elegans CDT-1, the Hox protein NOB-1, and the Six protein CEH-32. GMN-1 inhibits not only the interaction between mouse Cdt1 and Mcm6 but also licensing activity in Xenopus egg extracts. RNA interference-mediated reduction of GMN-1 is associated with enlarged germ nuclei with aberrant nucleolar morphology, severely impaired gametogenesis, and chromosome bridging in intestinal cells. We conclude that the Cdt1-geminin system is conserved throughout metazoans and that geminin has evolved in these taxa to regulate proliferation and differentiation by directly interacting with Cdt1 and homeobox proteins.