Li L, Ernsting B R, Wishart M J, Lohse D L, Dixon J E
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109-0606, USA.
J Biol Chem. 1997 Nov 21;272(47):29403-6. doi: 10.1074/jbc.272.47.29403.
In Saccharomyces cerevisiae the CDC14 gene is essential for cell cycle progression. Strains carrying the cdc14-1(ts) allele enter the cell cycle and arrest at restrictive temperatures. We have identified two human cDNAs encoding proteins which share sequence identity to the yeast CDC14p. The cell cycle arrest in cdc14-1(ts) can be specifically complemented by the human cDNAs suggesting that they are functionally equivalent to the yeast CDC14 gene. Another clone identified in the search for human CDC14-like proteins corresponded to the putative tumor suppressor gene PTEN/MMAC1 (phosphatase and tensin homologue deleted on chromosome 10 or mutated in multiple advanced cancers 1). Analysis of the PTEN/MMAC1 showed that it did not complement the cdc14-1(ts) allele and that it is more closely related to the yeast open reading frame YNL128W. Human CDC14p and PTEN/MMAC1 were expressed as recombinant proteins, and both were shown to have kinetic properties characteristic of dual specific phosphatases. The human CDC14p was localized in the nucleus while PTEN/MMAC1 has been reported to be localized in the cytoplasm. Our results suggest that CDC14 and YNL128W/PTEN/MMAC1 represent two related, but distinct, families of human and yeast phosphatases.
在酿酒酵母中，CDC14基因对于细胞周期进程至关重要。携带cdc14-1（ts）等位基因的菌株进入细胞周期后，在限制温度下会停滞生长。我们已经鉴定出两个人类cDNA，它们编码的蛋白质与酵母CDC14p具有序列同源性。cdc14-1（ts）中的细胞周期停滞可以被人类cDNA特异性互补，这表明它们在功能上等同于酵母CDC14基因。在寻找人类CDC14样蛋白的过程中鉴定出的另一个克隆对应于假定的肿瘤抑制基因PTEN/MMAC1（10号染色体上缺失或在多种晚期癌症中发生突变的磷酸酶和张力蛋白同源物）。对PTEN/MMAC1的分析表明，它不能互补cdc14-1（ts）等位基因，并且它与酵母开放阅读框YNL128W的关系更为密切。人类CDC14p和PTEN/MMAC1作为重组蛋白表达，并且两者都显示出具有双特异性磷酸酶的动力学特性。人类CDC14p定位于细胞核，而PTEN/MMAC1据报道定位于细胞质。我们的结果表明，CDC14和YNL128W/PTEN/MMAC1代表了人类和酵母磷酸酶的两个相关但不同的家族。
