Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation.
Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation.
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线虫中MPS1激酶的自然损失发现了螺旋样激酶1在纺锤体检查点开始中的作用。
DOI：
10.1016/j.celrep.2015.05.039
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发表时间：
2015-07-07
期刊：
影响因子：
8.8
通讯作者：
Abrieu A
中科院分区：
文献类型：
--
作者：
Espeut J;Lara-Gonzalez P;Sassine M;Shiau AK;Desai A;Abrieu A
纺锤体检查点通过防止后期开始直到所有染色体附着到纺锤体微管上来防止细胞分裂期间的染色体丢失。检查点信号产生于着丝粒，纺锤体微管在染色体上的主要附着位点。Mps 1激酶通过磷酸化着丝粒定位的支架蛋白Knl 1以产生Bub 1/Bub 3的磷酸对接位点来启动检查点信号传导。Mps 1是广泛保守的，但令人惊讶的是，在线虫谱系中不存在。在这里，我们表明，PLK-1，它的目标是一个类似的底物基序Mps 1，功能上取代Mps 1在C。elegans通过磷酸化KNL-1来指导BUB-1/BUB-3动粒募集。这一发现使我们重新检查了人类细胞中的检查点启动，我们发现Plk 1共抑制相对于单独的Mps 1抑制显著降低了Knl 1磷酸化和Bub 1动粒募集。因此，PLK-1在C. elegans揭示了Plk 1在具有Mps 1的物种中的作用。
The spindle checkpoint safeguards against chromosome loss during cell division by preventing anaphase onset until all chromosomes are attached to spindle microtubules. Checkpoint signal is generated at kinetochores, the primary attachment site on chromosomes for spindle microtubules. Mps1 kinase initiates checkpoint signaling by phosphorylating the kinetochore-localized scaffold protein Knl1 to create phospho-docking sites for Bub1/Bub3. Mps1 is widely conserved but is surprisingly absent from the nematode lineage. Here, we show that PLK-1, which targets a similar substrate motif as Mps1, functionally substitutes for Mps1 in C. elegans by phosphorylating KNL-1 to direct BUB-1/BUB-3 kinetochore recruitment. This finding led us to re-examine checkpoint initiation in human cells, where we found that Plk1 co-inhibition significantly reduced Knl1 phosphorylation and Bub1 kinetochore recruitment relative to Mps1 inhibition alone. Thus, the finding that PLK-1 functionally substitutes for Mps1 in checkpoint initiation in C. elegans uncovered a role for Plk1 in species that have Mps1.