Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery
复制标题
DOI：
10.1038/nature07185
复制
发表时间：
2008-09-04
期刊：
影响因子：
64.8
通讯作者：
Medema, Rene H.
中科院分区：
文献类型：
--
作者：
Macurek, Libor;Lindqvist, Arne;Medema, Rene H.
Polo样激酶-1（PLK 1）是一种重要的有丝分裂激酶，调节细胞分裂过程的多个方面（1）。PLK 1的激活需要PLK 1激酶结构域的T-环中保守的苏氨酸残基（Thr 210）的磷酸化，但负责此的激酶尚未被肯定地鉴定（2-6）。在这里，我们表明，在人类细胞PLK 1激活发生在进入有丝分裂前几个小时，并需要极光A（AURKA，也称为STK 6）依赖性磷酸化的Thr 210。我们发现极光A可以直接磷酸化Thr 210上的PLK 1，并且极光A对PLK 1的活性被极光A的已知辅因子Bora（也称为C13 orf 34和FLJ 22624）大大增强（参考文献7）。我们发现Bora/aurora-A依赖性磷酸化是PLK 1在检查点依赖性阻滞后促进有丝分裂进入的先决条件。重要的是，PLK 1-T210 D磷酸模拟突变体的表达部分克服了检查点恢复中对极光A的需求。总之，这些数据表明PLK 1的初始激活是极光A的主要功能。
Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process(1). Activation of PLK1 requires phosphorylation of a conserved threonine residue ( Thr 210) in the T- loop of the PLK1 kinase domain, but the kinase responsible for this has not yet been affirmatively identified(2-6). Here we show that in human cells PLK1 activation occurs several hours before entry into mitosis, and requires aurora A ( AURKA, also known as STK6)- dependent phosphorylation of Thr 210. We find that aurora A can directly phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is greatly enhanced by Bora ( also known as C13orf34 and FLJ22624), a known cofactor for aurora A ( ref. 7). We show that Bora/ aurora- A- dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint- dependent arrest. Importantly, expression of a PLK1- T210D phospho- mimicking mutant partially overcomes the requirement for aurora A in checkpoint recovery. Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A.