AURKA destruction is decoupled from its activity at mitotic exit but suppresses interphase activity
AURKA destruction is decoupled from its activity at mitotic exit but suppresses interphase activity
复制标题
AURKA 破坏与其有丝分裂出口时的活性脱钩，但抑制间期活性
DOI：
10.1101/850917
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Abdelbaki A
中科院分区：
文献类型：
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作者：
Abdelbaki A
AURKA的活性通过多种机制控制，包括磷酸化、泛素介导的降解和与TPX2的变构相互作用。在有丝分裂退出过程中，在AURKA被降解之前，活性在有丝分裂时达到峰值，这一过程严格依赖于APC/C共激活子FZR1。我们使用FZR1敲除细胞（FZR1KO）和一种新的基于fret的AURKA生物传感器来研究如何在不破坏的情况下调节活性。我们发现，尽管没有破坏，但在有丝分裂结束时，fzr1kcells中的AURKA活性与亲本细胞中的一样迅速下降。出乎意料的是，TPX2在fzr1koccells中正常降解。一个足以与AURKA结合但在有丝分裂结束时未降解的n端TPX2片段过表达导致AURKA失活延迟。我们得出结论，AURKA在有丝分裂结束时的失活不是由其自身的降解决定的，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反而抑制间期的AURKA活性，并且是有丝分裂后间期线粒体网络组装所必需的。
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 mitotic exit in a process strictly dependent on APC/C coactivator FZR1. We used FZR1 knockout cells (FZR1KO) and a novel FRET-based AURKA biosensor to investigate how activity is regulated in absence of destruction. We found that AURKA activity in FZR1KOcells dropped at mitotic exit as rapidly as in parental cells, despite absence of destruction. Unexpectedly, TPX2 was degraded normally in FZR1KOcells. Overexpression of an N-terminal TPX2 fragment sufficient for AURKA binding, but not degraded at mitotic exit, caused delay in AURKA inactivation. We conclude that AURKA inactivation in mitotic exit is determined not by its own degradation but by degradation of TPX2 and therefore 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.
影响因子：
4.7
作者：
Reboutier D;Benaud C;Prigent C
通讯作者：
Prigent C
DOI：
10.1083/jcb.201210060
发表时间：
2013-04-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Reboutier D;Troadec MB;Cremet JY;Chauvin L;Guen V;Salaun P;Prigent C
通讯作者：
Prigent C