Autophosphorylation of polo-like kinase 4 and its role in centriole duplication.
Autophosphorylation of polo-like kinase 4 and its role in centriole duplication.
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DOI：
10.1091/mbc.e09-06-0505
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发表时间：
2010-02-15
影响因子：
3.3
通讯作者：
Grand-Perret T
中科院分区：
文献类型：
--
作者：
Sillibourne JE;Tack F;Vloemans N;Boeckx A;Thambirajah S;Bonnet P;Ramaekers FC;Bornens M;Grand-Perret T
PLK 4是中心粒复制的关键调节因子。在这里，我们表明，PLK 4是积极的超越中心粒复制的启动与丰富的活性激酶增加到有丝分裂的峰值。重要的是，我们表明母子中心粒之间存在PLK 4丰度差异，并且活性PLK 4仅限于中心体。中心体复制以严格控制的方式在每个细胞周期发生一次。Polo样激酶4（PLK 4）是这一过程的关键调节因子，其激酶活性对中心粒复制至关重要。在这里，我们表明，丝氨酸S305的PLK 4自磷酸化是激酶激活的结果，并使活性组分在细胞中被识别。在G1/S期的复制母中心粒上可检测到活性PLK 4，活性激酶的比例通过间期增加，在有丝分裂中达到最大。PLK 4在复制子中心粒的激活被延迟到G2，但在M期达到与复制母中心粒相当的水平。活性PLK 4由蛋白酶体调节，因为蛋白酶体抑制或PLK 4的降解决定子基序的突变导致S305-磷酸化PLK 4的积累。自磷酸化可能在中心粒复制过程中起作用，因为模拟S305磷酸化增强了过表达的PLK 4诱导中心粒扩增的能力。重要的是，我们表明，S305-磷酸化PLK 4是专门隔离在中心体相反的非磷酸化形式。这些数据表明，PLK 4活性仅限于中心体，以防止异常的中心粒组装和持续的激酶活性所需的中心粒复制。
PLK4 is a key regulator of centriole duplication. Here, we show that PLK4 is active beyond the initiation of centriole duplication with the abundance of active kinase increasing to a peak in mitosis. Importantly, we show that differences in PLK4 abundance exist between mother and daughter centrioles and that active PLK4 is restricted to the centrosome. Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase activity is essential for centriole duplication. Here, we show that PLK4 autophosphorylation of serine S305 is a consequence of kinase activation and enables the active fraction to be identified in the cell. Active PLK4 is detectable on the replicating mother centriole in G1/S, with the proportion of active kinase increasing through interphase to reach a maximum in mitosis. Activation of PLK4 at the replicating daughter centriole is delayed until G2, but a level equivalent to the replicating mother centriole is achieved in M phase. Active PLK4 is regulated by the proteasome, because either proteasome inhibition or mutation of the degron motif of PLK4 results in the accumulation of S305-phosphorylated PLK4. Autophosphorylation probably plays a role in the process of centriole duplication, because mimicking S305 phosphorylation enhances the ability of overexpressed PLK4 to induce centriole amplification. Importantly, we show that S305-phosphorylated PLK4 is specifically sequestered at the centrosome contrary to the nonphosphorylated form. These data suggest that PLK4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication.
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影响因子：
7.8
作者：
KURIYAMA, R;BORISY, GG
通讯作者：
BORISY, GG
影响因子：
3
作者：
PAINTRAND, M;MOUDJOU, M;BORNENS, M
通讯作者：
BORNENS, M
影响因子：
3.3
作者：
Keller, Lani C.;Geimer, Stefan;Marshall, Wallace F.
通讯作者：
Marshall, Wallace F.
影响因子：
11.8
作者：
Kleylein-Sohn, Julia;Westendorf, Jens;Nigg, Erich A.
通讯作者：
Nigg, Erich A.
影响因子：
21.3
作者：
Habedanck, R;Stierhof, YD;Nigg, EA
通讯作者：
Nigg, EA