Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69117 Heidelberg, Germany.
J Cell Sci. 2010 Sep 1;123(Pt 17):2867-76. doi: 10.1242/jcs.074815.
CDC14 was originally identified by L. Hartwell in his famous screen for genes that regulate the budding yeast cell cycle. Subsequent work showed that Cdc14 belongs to a family of highly conserved dual-specificity phosphatases that are present in a wide range of organisms from yeast to human. Human CDC14B is even able to fulfill the essential functions of budding yeast Cdc14. In budding yeast, Cdc14 counteracts the activity of cyclin dependent kinase (Cdk1) at the end of mitosis and thus has important roles in the regulation of anaphase, mitotic exit and cytokinesis. On the basis of the functional conservation of other cell-cycle genes it seemed obvious to assume that Cdc14 phosphatases also have roles in late mitosis in mammalian cells and regulate similar targets to those found in yeast. However, analysis of the human Cdc14 proteins (CDC14A, CDC14B and CDC14C) by overexpression or by depletion using small interfering RNA (siRNA) has suggested functions that are quite different from those of ScCdc14. Recent studies in avian and human somatic cell lines in which the gene encoding either Cdc14A or Cdc14B had been deleted, have shown - surprisingly - that neither of the two phosphatases on its own is essential for viability, cell-cycle progression and checkpoint control. In this Commentary, we critically review the available data on the functions of yeast and vertebrate Cdc14 phosphatases, and discuss whether they indeed share common functions as generally assumed.
CDC14 最初是由 L. Hartwell 在他著名的筛选调控芽殖酵母细胞周期的基因的实验中发现的。随后的研究表明，Cdc14 属于高度保守的双特异性磷酸酶家族，存在于从酵母到人类等多种生物中。人类 CDC14B 甚至能够完成芽殖酵母 Cdc14 的基本功能。在芽殖酵母中，Cdc14 在有丝分裂末期拮抗细胞周期蛋白依赖性激酶（Cdk1）的活性，因此在调节后期、有丝分裂退出和胞质分裂中具有重要作用。基于其他细胞周期基因的功能保守性，人们很容易假设 Cdc14 磷酸酶在哺乳动物细胞的晚期有丝分裂中也有作用，并调节与酵母中发现的相似的靶标。然而，通过过表达或使用小干扰 RNA（siRNA）耗竭分析人类 Cdc14 蛋白（CDC14A、CDC14B 和 CDC14C）表明，其功能与 ScCdc14 截然不同。最近在禽类和人类体细胞系中的研究表明，编码 Cdc14A 或 Cdc14B 的基因缺失后，令人惊讶的是，两种磷酸酶中的任何一种单独都不是生存所必需的，细胞周期进程和检查点控制。在这篇评论中，我们批判性地回顾了关于酵母和脊椎动物 Cdc14 磷酸酶功能的现有数据，并讨论了它们是否确实像通常假设的那样具有共同的功能。
