Cdc14: a highly conserved family of phosphatases with non-conserved functions?
Cdc14: a highly conserved family of phosphatases with non-conserved functions?
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DOI：
10.1242/jcs.074815
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Schiebel, Elmar
中科院分区：
文献类型：
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作者：
Mocciaro, Annamaria;Schiebel, Elmar
CDC14最初是由L.Hartwell在他著名的基因筛查中发现的，该基因调节萌芽中的酵母细胞周期。随后的工作表明，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的广泛生物体中。人类CDC14B甚至能够完成萌芽酵母CDC14的基本功能。在芽殖酵母中，CDC14在有丝分裂结束时抵消细胞周期蛋白依赖性激酶(CDK1)的活性，因此在有丝分裂后期、有丝分裂退出和胞质分裂中具有重要的调节作用。根据其他细胞周期基因的功能保守性，似乎很明显地假设CDC14磷酸酶也在哺乳动物细胞的晚期有丝分裂中发挥作用，并调控与酵母中发现的相似的靶点。然而，通过使用小干扰RNA(SiRNA)过度表达或耗尽人类CDC14蛋白(CDC14A、CDC14B和CDC14C)的分析表明，其功能与ScCDc14的功能截然不同。最近在禽类和人类体细胞系中编码CDC14A或CDC14B基因缺失的研究表明，令人惊讶的是，这两种磷酸酶本身都不是生存、细胞周期进展和检查点控制所必需的。在这篇评论中，我们批判性地回顾了有关酵母和脊椎动物CDC14磷酸酶功能的现有数据，并讨论它们是否真的像通常假设的那样具有共同的功能。
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.