磷酸化调节 p31Comet-有丝分裂阻滞缺陷 2（Mad2）相互作用，以促进纺锤体检查点（SAC）活性。
Phosphorylation regulates the p31Comet-mitotic arrest-deficient 2 (Mad2) interaction to promote spindle assembly checkpoint (SAC) activity.
机构信息
Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195.
Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195.
出版信息
J Biol Chem. 2014 Apr 18;289(16):11367-11373. doi: 10.1074/jbc.M113.520841. Epub 2014 Mar 4.
Abstract
The spindle assembly checkpoint (SAC) ensures the faithful segregation of the genome during mitosis by ensuring that sister chromosomes form bipolar attachments with microtubules of the mitotic spindle. p31(Comet) is an antagonist of the SAC effector Mad2 and promotes silencing of the SAC and mitotic progression. However, p31(Comet) interacts with Mad2 throughout the cell cycle. We show that p31(Comet) binds Mad2 solely in an inhibitory manner. We demonstrate that attenuating the affinity of p31(Comet) for Mad2 by phosphorylation promotes SAC activity in mitosis. Specifically, phosphorylation of Ser-102 weakens p31(Comet)-Mad2 binding and enhances p31(Comet)-mediated bypass of the SAC. Our results provide the first evidence for regulation of p31(Comet) and demonstrate a previously unknown event controlling SAC activity.
摘要
纺锤体组装检查点（SAC）通过确保姐妹染色体与有丝分裂纺锤体的微管形成双极连接，确保了基因组在有丝分裂过程中的忠实分离。p31（Comet）是 SAC 效应物 Mad2 的拮抗剂，可促进 SAC 的沉默和有丝分裂的进行。然而，p31（Comet）在整个细胞周期中都与 Mad2 相互作用。我们表明，p31（Comet）仅以抑制方式结合 Mad2。我们证明，通过磷酸化来减弱 p31（Comet）与 Mad2 的亲和力可促进有丝分裂中的 SAC 活性。具体而言，丝氨酸 102 的磷酸化会削弱 p31（Comet）-Mad2 结合，并增强 p31（Comet）介导的绕过 SAC。我们的结果为 p31（Comet）的调节提供了第一个证据，并证明了一个以前未知的控制 SAC 活性的事件。
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