Two p90 Ribosomal S6 Kinase Isoforms Are Involved in the Regulation of Mitotic and Meiotic Arrest in Artemia
Two p90 Ribosomal S6 Kinase Isoforms Are Involved in the Regulation of Mitotic and Meiotic Arrest in Artemia
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两种 p90 核糖体 S6 激酶亚型参与丰年虫有丝分裂和减数分裂停滞的调节
DOI：
10.1074/jbc.m114.553370
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发表时间：
2014-06-06
影响因子：
4.8
通讯作者：
Yang, Wei-Jun
中科院分区：
文献类型：
--
作者：
Duan, Ru-Bing;Zhang, Li;Yang, Wei-Jun
P90核糖体S6激酶(RSK)有多种异构体，调节细胞生长、增殖、成熟和运动等多种细胞功能。然而，RSK异构体的结构和功能之间的关系仍未确定。卤虫是研究细胞周期停滞的有用模型，因为这些动物经历了长时间的滞育，一种强制休眠状态。在卤虫中发现了一种新的RSK亚型，命名为Ar-RSK2。将该亚型与我们以前在卤虫中发现的一种RSK亚型进行了比较，命名为ar-Rsk1。AR-RSK2具有ERK对接基序，而Ar-Rsk1没有。Western印迹分析表明，Ar-Rsk1被磷酸化激活，从而阻止了卵母细胞的减数分裂。Ar-Rsk1基因的敲除降低了磷酸化cdc2的水平，从而抑制了细胞抑制因子的活性。这表明Ar-Rsk1调控细胞减数分裂中的细胞抑制因子。在有丝分裂受阻的卤虫包囊中，AR-RSK2表达下调。Ar-RSK2基因敲除后，细胞周期蛋白D3和组蛋白H3的磷酸化水平降低，并产生假性滞育孢子。这表明Ar-RSK2调控有丝分裂停滞。PLK和ERK RNAi结果表明，在卤虫中，PLK-ERK可以激活Ar-RSK2，但不能激活Ar-Rsk1。这是第一次报道具有和不具有ERK对接基序的RSK亚型分别调节有丝分裂和减数分裂。这项研究为了解RSK亚型的结构和功能之间的关系提供了洞察力。
There are multiple isoforms of p90 ribosomal S6 kinase (RSK), which regulate diverse cellular functions such as cell growth, proliferation, maturation, and motility. However, the relationship between the structures and functions of RSK isoforms remains undetermined. Artemia is a useful model in which to study cell cycle arrest because these animals undergo prolonged diapauses, a state of obligate dormancy. A novel RSK isoform was identified in Artemia, which was termed Ar-Rsk2. This isoform was compared with an RSK isoform that we previously identified in Artemia, termed Ar-Rsk1. Ar-Rsk2 has an ERK-docking motif, whereas Ar-Rsk1 does not. Western blot analysis revealed that Ar-Rsk1 was activated by phosphorylation, which blocked meiosis in oocytes. Knockdown of Ar-Rsk1 reduced the level of phosphorylated cdc2 and thereby suppressed cytostatic factor activity. This indicates that Ar-Rsk1 regulates the cytostatic factor in meiosis. Expression of Ar-Rsk2 was down-regulated in Artemia cysts in which mitosis was arrested. Knockdown of Ar-Rsk2 resulted in decreased levels of cyclin D3 and phosphorylated histone H3, and the production of pseudo-diapause cysts. This indicates that Ar-Rsk2 regulates mitotic arrest. PLK and ERK RNAi showed that Ar-Rsk2, but not Ar-Rsk1, could be activated by PLK-ERK in Artemia. This is the first study to report that RSK isoforms with and without an ERK-docking motif regulate mitosis and meiosis, respectively. This study provides insight into the relationship between the structures and functions of RSK isoforms.