An essential protease involved in bacterial cell-cycle control

An essential protease involved in bacterial cell-cycle control
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DOI:
10.1093/emboj/17.19.5658
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发表时间:
1998-10-01
期刊:
影响因子:
11.4
通讯作者:
Fuchs, T
Fuchs, T
中科院分区:
生物学1区
文献类型:
--
作者:
Jenal, U;Fuchs, T

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关键调节蛋白的蛋白水解失活在真核生物细胞周期控制中是必不可少的。我们已经在真细菌中发现了一种蛋白酶,它对生存能力和细胞周期进程是必不可少的,这表明蛋白质水解也参与控制细菌的细胞周期。缺乏atp依赖性丝氨酸蛋白酶ClpXP的Caulobacter突变体在染色体复制开始之前被阻滞在细胞周期中,并在细胞分裂过程中被阻断。ClpXP由两种类型的多肽组成,ClpX atp酶和ClpP肽酶,ClpP催化活性丝氨酸残基的定点突变证实了ClpXP的蛋白质水解活性是必不可少的,缺乏ClpX或ClpP的突变体的分析显示,这两种蛋白质都是体内调节蛋白CtrA的细胞周期依赖性降解所必需的。CtrA是双组分信号转导系统的反应调节家族成员,控制着Caulobacter的多个细胞周期过程,特别是CtrA负性控制DNA复制,我们的研究结果表明,ClpXP蛋白酶对CtrA蛋白的特异性降解有助于该生物体内G(1)到s的转化。
Proteolytic inactivation of key regulatory proteins is essential in eukaryotic cell-cycle control. We have identified a protease in the eubacterium Caulobacter crescentus that is indispensable for viability and cell-cycle progression, indicating that proteolysis is also involved in controlling the bacterial cell cycle, Mutants of Caulobacter that lack the ATP-dependent serine protease ClpXP are arrested in the cell cycle before the initiation of chromosome replication and are blocked in the cell division process. ClpXP is composed of two types of polypeptides, the ClpX ATPase and the ClpP peptidase, Site-directed mutagenesis of the catalytically active serine residue of ClpP confirmed that the proteolytic activity of ClpXP is essential, Analysts of mutants lacking ClpX or ClpP revealed that both proteins are required in vivo for the cell-cycle-dependent degradation of the regulatory protein CtrA, CtrA is a member of the response regulator family of two-component signal transduction systems and controls multiple cell-cycle processes in Caulobacter, In particular, CtrA negatively controls DNA replication and our findings suggest that specific degradation of the CtrA protein by the ClpXP protease contributes to G(1)-to-S transition in this organism.