Phosphorylation of the Oxytricha telomere protein: possible cell cycle regulation.
Phosphorylation of the Oxytricha telomere protein: possible cell cycle regulation.
复制标题
氧化毛虫端粒蛋白的磷酸化：可能的细胞周期调节。
DOI：
10.1093/nar/23.11.1887
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发表时间：
1995
影响因子：
14.9
通讯作者：
Cech,TR
中科院分区：
文献类型：
--
作者：
Hicke,B;Rempel,R;Maller,J;Swank,RA;Hamaguchi,JR;Bradbury,EM;Prescott,DM;Cech,TR
在纤毛虫Oxytricha nova的大核中，端粒末端是单链（T4 G4）2DNA，与异二聚体端粒蛋白（αβ）结合。在非同步生长的尖毛藻中，α和β亚基（α-TP和β-TP）都被磷酸化，β-TP被磷酸化的程度更高，在体外，小鼠细胞周期蛋白依赖性激酶（Cdks）磷酸化β-TP的赖氨酸-rlch结构域，该结构域不是特异性DNA结合所必需的，但与端粒的高级结构形成有关。因此，β-TP的磷酸化可以调节端粒蛋白的功能，这与特异性DNA结合无关。磷酸化氨基酸分析表明，小鼠Cdks主要修饰β-TP中的苏氨酸残基，这与β-TP含有两个含有苏氨酸残基的共有Cdk识别序列的观察结果一致。在Xenopusegg细胞周期提取物中，β-TP在M期被磷酸化，在间期被去磷酸化。这项工作提供了第一个直接证据磷酸化在端粒在任何生物，以及间接证据细胞周期调控端粒磷酸化。Cdc 2/细胞周期蛋白A和Cdc 2/细胞周期蛋白B激酶是主要分裂事件所必需的。一个有吸引力的模型是，在细胞核分裂之前，这些激酶对β-TP的磷酸化是破坏端粒相互之间和/或与细胞核结构的结合所必需的。
In the macronucleus of the ciliateOxytricha nova, telomeres end with single-stranded (T4G4)2DNA bound to a heterodimeric telomeVe protein (αβ). Both the α and β subunits (α-TP and β-TP) were phosphory-lated in asynchronously growingOxytricha; β-TP was phosphorylated to a much higher degree.In vitro, mouse cyclIn-dependent kineses (Cdks) phosphory-lated β-TP In a lyslne-rlch domain that Is not required for specific DNA binding but is implicated in higher order structure formation of telomeres. Therefore, phosphorylation of β-TP could modulate a function of the telomere protein that is separate from specific DNA binding. Phosphoamino acid analysis revealed that the mouse Cdks modify predominantly threonlne residues in β-TP, consistent with the observation that β-TP contains two consensus Cdk recognition sequences containing threonlne residues. InXenopusegg extracts that undergo cell cycling, β-TP was phos-phorylated In M phase and dephosphorylated In interphase. This work provides the first direct evidence of phosphorylation at telomeres in any organism, as well as indirect evidence for cell cycle regulation of telomere phosphorylation. The Cdc2/cyclin A and Cdc2/cyclin B kinases are required for major m It otic events. An attractive model is that phosphorylation of β-TP by these kinases is required for the breakdown of telomere associations with each other and/or with nuclear structures prior to nuclear division.