LIN-9 phosphorylation on threonine-96 is required for transcriptional activation of LIN-9 target genes and promotes cell cycle progression.
LIN-9 phosphorylation on threonine-96 is required for transcriptional activation of LIN-9 target genes and promotes cell cycle progression.
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DOI：
10.1371/journal.pone.0087620
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Colamonici OR
中科院分区：
文献类型：
--
作者：
Eckerdt F;Perez-Neut M;Colamonici OR
细胞周期转变由细胞周期蛋白的及时表达控制，细胞周期蛋白是细胞周期蛋白依赖性激酶 (Cdks) 的激活亚基，负责口袋蛋白的失活。细胞周期蛋白的过度表达会促进细胞增殖和癌症。因此，了解细胞周期蛋白调节细胞周期促进基因（包括后续细胞周期蛋白）表达的机制非常重要。 LIN-9 以及口袋蛋白 p107 和 p130 是 DREAM 复合体的成员，该复合体在 G0 期抑制细胞周期基因。有趣的是，我们对Cyclin D/Cdk4磷酸化p107、p130在G1早期分解DREAM复合体后LIN-9的调控和功能知之甚少。在本报告中，我们证明了细胞周期蛋白 E1/Cdk3 在 Thr-96 上磷酸化 LIN-9。将 Thr-96 突变为丙氨酸会抑制细胞周期蛋白 A2 和 B1 启动子的激活，而拟磷化 Asp 突变体会强烈激活其启动子并触发 293T 细胞加速进入 G2/M 期。综上所述，我们的数据表明细胞周期蛋白 E1 在 G1/S 期之后进入 S/G2 期具有新的作用，很可能是通过 LIN-9 诱导后续细胞周期蛋白 A2 和 B1 的表达。
Cell cycle transitions are governed by the timely expression of cyclins, the activating subunits of Cyclin-dependent kinases (Cdks), which are responsible for the inactivation of the pocket proteins. Overexpression of cyclins promotes cell proliferation and cancer. Therefore, it is important to understand the mechanisms by which cyclins regulate the expression of cell cycle promoting genes including subsequent cyclins. LIN-9 and the pocket proteins p107 and p130 are members of the DREAM complex that in G0 represses cell cycle genes. Interestingly, little is know about the regulation and function of LIN-9 after phosphorylation of p107,p130 by Cyclin D/Cdk4 disassembles the DREAM complex in early G1. In this report, we demonstrate that cyclin E1/Cdk3 phosphorylates LIN-9 on Thr-96. Mutating Thr-96 to alanine inhibits activation of cyclins A2 and B1 promoters, whereas a phosphomimetic Asp mutant strongly activates their promoters and triggers accelerated entry into G2/M phase in 293T cells. Taken together, our data suggest a novel role for cyclin E1 beyond G1/S and into S/G2 phase, most likely by inducing the expression of subsequent cyclins A2 and B1 through LIN-9.
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影响因子：
8
作者：
Knight, A. S.;Notaridou, M.;Watson, R. J.
通讯作者：
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影响因子：
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