Molecular Biology of Centrosomes and Cilia Unit, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
J Cell Sci. 2012 Jul 1;125(Pt 13):3091-6. doi: 10.1242/jcs.106021. Epub 2012 Mar 27.
In Saccharomyces cerevisiae the Cdc14 phosphatase plays a well-established role in reverting phosphorylation events on substrates of the mitotic cyclin-dependent kinase (M-Cdk1), thereby promoting mitotic exit and downregulation of M-Cdk1 activity. Cdc14 localizes at the site of cell cleavage after M-Cdk1 inactivation, suggesting that Cdc14 may perform a crucial, yet ill-defined, role during cytokinesis. Here, we identified Inn1, as a novel direct substrate of both M-Cdk1 and Cdc14. Cdc14 colocalizes with Inn1 at the cell division site and interacts with the C-terminal proline-rich domain of Inn1 that mediates its binding to the SH3-domain-containing proteins Hof1 and Cyk3. We show that phosphorylation of Inn1 by Cdk1 partially perturbs the interaction of Inn1 with Cyk3 thereby reducing the levels of Cyk3 at the cell division site. We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis.
在酿酒酵母中，Cdc14 磷酸酶在逆转有丝分裂细胞周期蛋白依赖性激酶 (M-Cdk1) 底物的磷酸化事件方面发挥着既定的作用，从而促进有丝分裂退出和 M-Cdk1 活性的下调。Cdc14 在 M-Cdk1 失活后定位于细胞分裂部位，这表明 Cdc14 可能在胞质分裂过程中发挥着关键但定义不明确的作用。在这里，我们鉴定出 Inn1 是 M-Cdk1 和 Cdc14 的一个新的直接底物。Cdc14 与 Inn1 在细胞分裂部位共定位，并与 Inn1 的 C 端富含脯氨酸的结构域相互作用，该结构域介导其与 SH3 结构域蛋白 Hof1 和 Cyk3 的结合。我们表明，Cdk1 对 Inn1 的磷酸化部分破坏了 Inn1 与 Cyk3 的相互作用，从而降低了细胞分裂部位的 Cyk3 水平。我们提出 Cdc14 拮抗 Cdk1 对 Inn1 的磷酸化作用，以促进 Inn1-Cyk3 复合物的形成，从而促进胞质分裂。
