Activity of AURKA is controlled through multiple mechanisms including phosphorylation, ubiquitin-mediated degradation and allosteric interaction with TPX2. Activity peaks at mitosis, before AURKA is degraded during and after mitotic exit in a process strictly dependent on the APC/C coactivator FZR1. We used FZR1 knockout cells (FZR1^KO) and a novel FRET-based AURKA biosensor to investigate how AURKA activity is regulated in the absence of destruction. We found that AURKA activity in FZR1^KO cells dropped at mitotic exit as rapidly as in parental cells, despite absence of AURKA destruction. Unexpectedly, TPX2 was degraded normally in FZR1^KO cells. Overexpression of an N-terminal TPX2 fragment sufficient for AURKA binding, but that is not degraded at mitotic exit, caused delay in AURKA inactivation. We conclude that inactivation of AURKA at mitotic exit is determined not by AURKA degradation but by degradation of TPX2 and therefore is dependent on CDC20 rather than FZR1. The biosensor revealed that FZR1 instead suppresses AURKA activity in interphase and is critically required for assembly of the interphase mitochondrial network after mitosis.

This article has an associated First Person interview with the first authors of the paper.

AURKA 的活性通过多种机制控制，包括磷酸化、泛素介导的降解以及与 TPX2 的变构相互作用。活性在有丝分裂时达到峰值，之后 AURKA 在有丝分裂退出期间和之后被降解，该过程严格依赖于 APC/C 共激活剂 FZR1。我们使用 FZR1 敲除细胞 (FZR1 ^KO ) 和一种新型基于 FRET 的 AURKA 生物传感器来研究在没有破坏的情况下如何调节 AURKA 活性。我们发现，尽管没有 AURKA 破坏，但 FZR1 ^KO细胞中的 AURKA 活性在有丝分裂退出时与亲本细胞一样迅速下降。^{出乎意料的是，TPX2 在 FZR1 KO}细胞中正常降解。N 端 TPX2 片段的过度表达足以与 AURKA 结合，但在有丝分裂退出时不会降解，导致 AURKA 失活延迟。我们得出结论，AURKA 在有丝分裂出口处的失活不是由 AURKA 降解决定的，而是由 TPX2 的降解决定的，因此依赖于 CDC20 而不是 FZR1。生物传感器显示，FZR1 相反会抑制间期的 AURKA 活性，并且是有丝分裂后间期线粒体网络组装所必需的。

本文与该论文的第一作者进行了相关的第一人称采访。