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首页> 外文期刊>Molecular and Cellular Biology >Cpc2, a Fission Yeast Homologue of Mammalian RACK1 Protein, Interacts with Ran1 (Pat1) Kinase To Regulate Cell Cycle Progression and Meiotic Development
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Cpc2, a Fission Yeast Homologue of Mammalian RACK1 Protein, Interacts with Ran1 (Pat1) Kinase To Regulate Cell Cycle Progression and Meiotic Development

机译：Cpc2，哺乳动物RACK1蛋白的裂变酵母同源物，与Ran1（Pat1）激酶相互作用，调节细胞周期进程和减数分裂发育。

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The Schizosaccharomyces pombe ran1/pat1 gene regulates the transition between mitosis and meiosis. Inactivation of Ran1 (Pat1) kinase is necessary and sufficient for cells to exit the cell cycle and undergo meiosis. The yeast two-hybrid interaction trap was used to identify protein partners for Ran1/Pat1. Here we report the identification of one of these, Cpc2. Cpc2 encodes a homologue of RACK1, a WD protein with homology to the β subunit of heterotrimeric G proteins. RACK1 is a highly conserved protein, although its function remains undefined. In mammalian cells, RACK1 physically associates with some signal transduction proteins, including Src and protein kinase C. Fission yeast cells containing a cpc2 null allele are viable but cell cycle delayed. cpc2Δ cells fail to accumulate in G1 when starved of nitrogen. This leads to defects in conjugation and meiosis. Copurification studies show that although Cpc2 and Ran1 (Pat1) physically associate, Cpc2 does not alter Ran1 (Pat1) kinase activity in vitro. Using a Ran1 (Pat1) fusion to green fluorescent protein, we show that localization of the kinase is impaired in cpc2Δ cells. Thus, in parallel with the proposed role of RACK1 in mammalian cells, fission yeast cpc2 may function as an anchoring protein for Ran1 (Pat1) kinase. All defects associated with loss of cpc2 are reversed in cells expressing mammalian RACK1, demonstrating that the fission yeast and mammalian gene products are indeed functional homologues.
机译：粟酒裂殖酵母ran1 / pat1 基因调节有丝分裂和减数分裂之间的过渡。 Ran1（Pat1）激酶的失活是必要的，并且足以使细胞退出细胞周期并减数分裂。酵母双杂交相互作用陷阱用于识别Ran1 / Pat1的蛋白质伴侣。在这里，我们报告其中之一Cpc2的标识。 Cpc2编码RACK1的同源物，RACK1是与异三聚体G蛋白的β亚基同源的WD蛋白。 RACK1是一种高度保守的蛋白，尽管其功能尚不清楚。在哺乳动物细胞中，RACK1与某些信号转导蛋白物理结合，包括Src和蛋白激酶C。含有 cpc2 无效等位基因的裂变酵母细胞是可行的，但细胞周期延迟。缺乏氮时， cpc2 Δ细胞无法在G 1 中积累。这导致共轭和减数分裂的缺陷。共纯化研究表明，尽管 Cpc2 和Ran1（Pat1）在物理上缔合，但Cpc2不会在体外改变Ran1（Pat1）激酶的活性。使用Ran1（Pat1）融合到绿色荧光蛋白上，我们表明在 cpc2 Δ细胞中该激酶的定位受到损害。因此，与拟议的RACK1在哺乳动物细胞中的作用平行，裂变酵母 cpc2 可能充当Ran1（Pat1）激酶的锚定蛋白。在表达哺乳动物RACK1的细胞中，与 cpc2 缺失相关的所有缺陷均被逆转，表明裂变酵母和哺乳动物基因产物的确是功能同源物。

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