Speedy/Ringo C regulates S and G2 phase progression in human cells.
Speedy/Ringo C regulates S and G2 phase progression in human cells.
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DOI：
10.4161/cc.7.19.6736
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发表时间：
2008-10
期刊：
影响因子：
4.3
通讯作者：
Solomon, Mark J.
中科院分区：
文献类型：
--
作者：
Cheng, Aiyang;Solomon, Mark J.
细胞周期蛋白依赖性激酶（CDKs）控制着细胞周期的转变和进展。除了通过与细胞周期蛋白结合而激活外，CDKs还可以通过与一类不相关的细胞周期调节因子（称为Speedy/Ringo （S/R）蛋白）结合而激活。尽管哺乳动物含有至少五种不同的Speedy/Ringo同源物，但这一不断增长的CDK激活物家族成员的具体功能在很大程度上仍然未知。我们研究了人类Speedy/Ringo C在HEK293细胞中的细胞周期作用。通过RNA干扰下调Speedy/Ringo C可延缓S和G2的进展，而异位表达则具有相反的作用，可减少S和G2/M的数量。双胸腺嘧啶阻滞和释放实验表明，过表达Speedy/Ringo C促进S期晚期进展。采用新颖的三色FACS方法测定G2期的长度，我们发现RNAi抑制Speedy/Ringo C可使G2期延长~30 min，而异位表达Speedy/Ringo C可使G2期缩短~25 min。此外，Speedy/Ringo C的过表达破坏了G2 DNA损伤检查点，增加了细胞死亡，并导致g1到s转变的细胞周期延迟。这些观察结果表明，CDK-Speedy/Ringo C复合物在细胞周期的S晚期和G2期积极调节细胞周期进程。
Cyclin-dependent kinases (CDKs) control cell cycle transitions and progression. In addition to their activation via binding to cyclins, CDKs can be activated via binding to an unrelated class of cell cycle regulators termed Speedy/Ringo (S/R) proteins. Although mammals contain at least five distinct Speedy/Ringo homologues, the specific functions of members of this growing family of CDK activators remain largely unknown. We investigated the cell cycle roles of human Speedy/Ringo C in HEK293 cells. Down-regulation of Speedy/Ringo C by RNA interference delayed S and G2 progression whereas ectopic expression had the opposite effect, reducing S and G2/M populations. Double thymidine arrest and release experiments showed that overexpression of Speedy/Ringo C promoted late S phase progression. Using a novel three-color FACS protocol to determine the length of G2phase, we found that the suppression of Speedy/Ringo C by RNAi prolonged G2 phase by ~30 min whereas ectopic expression of Speedy/Ringo C shortened G2 phase by ~25 min. In addition, overexpression of Speedy/Ringo C disrupted the G2 DNA damage checkpoint, increased cell death and caused a cell cycle delay at the G1-to-S transition. These observations indicate that CDK-Speedy/Ringo C complexes positively regulate cell cycle progression during the late S and G2 phases of the cell cycle.
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DOI：
10.1083/jcb.134.4.963
发表时间：
1996-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jin P;Gu Y;Morgan DO
通讯作者：
Morgan DO
影响因子：
7.5
作者：
Morgan, DO
通讯作者：
Morgan, DO
影响因子：
3.3
作者：
Porter, LA;Kong-Beltran, M;Donoghue, DJ
通讯作者：
Donoghue, DJ
影响因子：
4.1
作者：
Dinarina, A;Perez, LH;Nebreda, AR
通讯作者：
Nebreda, AR
影响因子：
10.5
作者：
Ferby, I;Blazquez, M;Nebreda, AR
通讯作者：
Nebreda, AR