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当大多数着丝粒未附着时，Chk2 可阻止有丝分裂退出。

Chk2 prevents mitotic exit when the majority of kinetochores are unattached.

机构信息

Department of Biology, University of Crete, Heraklion 70013, Greece.

出版信息

J Cell Biol. 2014 May 12;205(3):339-56. doi: 10.1083/jcb.201310071. Epub 2014 May 5.

DOI:10.1083/jcb.201310071
PMID:24798733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4018780/
Abstract

The spindle checkpoint delays exit from mitosis in cells with spindle defects. In this paper, we show that Chk2 is required to delay anaphase onset when microtubules are completely depolymerized but not in the presence of relatively few unattached kinetochores. Mitotic exit in Chk2-deficient cells correlates with reduced levels of Mps1 protein and increased Cdk1-tyrosine 15 inhibitory phosphorylation. Chk2 localizes to kinetochores and is also required for Aurora B-serine 331 phosphorylation in nocodazole or unperturbed early prometaphase. Serine 331 phosphorylation contributed to prometaphase accumulation in nocodazole after partial Mps1 inhibition and was required for spindle checkpoint establishment at the beginning of mitosis. In addition, expression of a phosphomimetic S331E mutant Aurora B rescued chromosome alignment or segregation in Chk2-deficient cells. We propose that Chk2 stabilizes Mps1 and phosphorylates Aurora B-serine 331 to prevent mitotic exit when most kinetochores are unattached. These results highlight mechanisms of an essential function of Chk2 in mitosis.

摘要

纺锤体检验点会延迟有纺锤体缺陷的细胞退出有丝分裂。在本文中，我们表明，当微管完全解聚时，Chk2 是延迟后期起始所必需的，但在相对较少的无附着动粒的情况下则不需要。Chk2 缺陷细胞的有丝分裂退出与 Mps1 蛋白水平降低和 Cdk1 酪氨酸 15 抑制性磷酸化增加有关。Chk2 定位于动粒上，在长春花碱或早期无干扰的前中期也需要 Aurora B-丝氨酸 331 磷酸化。丝氨酸 331 磷酸化有助于长春花碱抑制部分 Mps1 后在前期的积累，并且在有丝分裂开始时建立纺锤体检验点是必需的。此外，表达一种磷酸模拟 S331E 突变型 Aurora B 可挽救 Chk2 缺陷细胞中的染色体排列或分离。我们提出，Chk2 稳定 Mps1 并磷酸化 Aurora B-丝氨酸 331，以防止大多数动粒未附着时有丝分裂退出。这些结果突出了 Chk2 在有丝分裂中的基本功能的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/b518e7673f85/JCB_201310071_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/744d1d034e0b/JCB_201310071_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/6e80fe32aa90/JCB_201310071_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/566e3826c8ba/JCB_201310071_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/0320de653337/JCB_201310071_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/2ea68ab9389b/JCB_201310071_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/3466ed3f7eff/JCB_201310071_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/9aacae58a5d4/JCB_201310071_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/b518e7673f85/JCB_201310071_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/744d1d034e0b/JCB_201310071_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/6e80fe32aa90/JCB_201310071_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/566e3826c8ba/JCB_201310071_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/0320de653337/JCB_201310071_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/2ea68ab9389b/JCB_201310071_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/3466ed3f7eff/JCB_201310071_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/9aacae58a5d4/JCB_201310071_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/4018780/b518e7673f85/JCB_201310071_Fig8.jpg

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