Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase.
Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase.
复制标题
TOR 复合物 1 的突变通过 Glc7/PP1 磷酸酶抑制温度敏感的 ipl1-2/Aurora B 突变。
DOI：
10.1073/pnas.1014406108
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发表时间：
2011
影响因子：
11.1
通讯作者：
Tatchell K
中科院分区：
文献类型：
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作者：
Tatchell K
Ipl 1/Aurora B是染色体分离和核分裂所需的复合物的催化亚基。在分裂后期之前，Ipl 1定位于着丝粒，在那里需要建立适当的着丝粒-微管协会和调节纺锤体组装检查点。蛋白磷酸酶Glc 7/PP 1反对Ipl 1的一些这些活动。为了更彻底地表征对抗Ipl 1的Glc 7磷酸酶，我们已经鉴定了抑制anipl 1 - 2突变体的热敏性的突变。除了先前与ipl 1抑制相关的基因突变外，我们在TCO 89中发现了一个无效突变体，该突变体编码TOR复合物1（TORC 1）的一个亚基，该亚基是一种保守的雷帕霉素敏感激酶活性，可调节细胞对营养状况的反应。p11 - 2的温度敏感性也可以通过TOR 1的无效突变或通过施用药理学TORC 1抑制剂来抑制，表明TORC 1活性降低是抑制的原因。ipl 1 - 2生长缺陷的抑制伴随着染色体分离的保真度增加和Ipl 1底物组蛋白H3和Dam 1的磷酸化增加。atco 89突变体的细胞核Glc 7水平降低，表明G1 c7的细胞核积累需要TORC 1活性。此外，几个抑制p11 - 2温度敏感性的突变体GLC 7等位基因与TORC 1突变体表现出负的合成遗传相互作用。总之，我们的研究结果表明，TORC 1积极调节Glc 7的活动，反对Ipl 1，并提供了一种机制，以配合营养状况与有丝分裂调节。
Ipl1/Aurora B is the catalytic subunit of a complex that is required for chromosome segregation and nuclear division. Before anaphase, Ipl1 localizes to kinetochores, where it is required to establish proper kinetochore–microtubule associations and regulate the spindle assembly checkpoint. The protein phosphatase Glc7/PP1 opposes Ipl1 for some of these activities. To more thoroughly characterize the Glc7 phosphatase that opposes Ipl1, we have identified mutations that suppress the thermosensitivity of anipl1-2mutant. In addition to mutations in genes previously associated withipl1suppression, we recovered a null mutant inTCO89, which encodes a subunit of the TOR complex 1 (TORC1), the conserved rapamycin-sensitive kinase activity that regulates cell growth in response to nutritional status. The temperature sensitivity ofipl1-2can also be suppressed by null mutation ofTOR1or by administration of pharmacological TORC1 inhibitors, indicating that reduced TORC1 activity is responsible for the suppression. Suppression of theipl1-2growth defect is accompanied by increased fidelity of chromosome segregation and increased phosphorylation of the Ipl1 substrates histone H3 and Dam1. Nuclear Glc7 levels are reduced in atco89mutant, suggesting that TORC1 activity is required for the nuclear accumulation of Glc7. In addition, several mutantGLC7alleles that suppress the temperature sensitivity ofipl1-2exhibit negative synthetic genetic interactions with TORC1 mutants. Together, our results suggest that TORC1 positively regulates the Glc7 activity that opposes Ipl1 and provide a mechanism to tie nutritional status with mitotic regulation.