Involvement of p90 ribosomal S6 kinase in termination of cell cycle arrest during development of Artemia-encysted embryos
Involvement of p90 ribosomal S6 kinase in termination of cell cycle arrest during development of Artemia-encysted embryos
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DOI：
10.1074/jbc.m707853200
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发表时间：
2008-01-18
影响因子：
4.8
通讯作者：
Yang, Wei-Jun
中科院分区：
文献类型：
--
作者：
Dai, Jie-Qiong;Zhu, Xiao-Jing;Yang, Wei-Jun
为了应对各种环境威胁，Artemia已经进化出了一种独特的囊胚发育模式。从原肠期到孕前发育阶段，细胞分裂完全停止。然而，其分子机制尚不清楚。我们的研究集中在p90核糖体S6激酶（RSK）的参与，丝氨酸/苏氨酸激酶介导的丝裂原激活蛋白激酶级联下游信号转导，在胚胎后发育过程中终止细胞周期阻滞。通过免疫化学、形态学和细胞周期分析，鉴定出的Artemia RSK在胚胎后期和幼虫早期发育阶段被特异性激活，当被包裹胚胎的细胞恢复有丝分裂时。在体内，通过RNA干扰、激酶抑制和抗体中和来降低RSK活性，会导致外骨骼和内部组织之间存在明显间隙的缺陷幼虫。在这些异常个体中，检测到受影响区域的有丝分裂在很大程度上受到抑制。这些结果表明，在青蒿发育过程中需要RSK活性，并提示其在终止细胞周期（G(2)/M期）、阻滞和促进有丝分裂发生中起作用。因此，我们的研究结果可能为青蒿胚胎后发育过程中细胞分裂的调控提供见解，并揭示RSK功能的进一步方面。
Artemia has evolved a unique developmental pattern of encysted embryos to cope with various environmental threats. Cell divisions totally cease during the preemergence developmental stage from gastrula to prenauplius. The molecular mechanism of this, however, remains unknown. Our study focuses on the involvement of p90 ribosomal S6 kinase (RSK), a family of serine/threonine kinase-mediating signal transduction downstream of mitogen-activated protein kinase cascades, in the termination of cell cycle arrest during the post-embryonic development of Artemia-encysted gastrula. With immunochemistry, morphology, and cell cycle analysis, the identified Artemia RSK was established to be specifically activated during the post-embryonic and early larval developmental stages when arrested cells of encysted embryos resumed mitoses. In vivo knockdown of RSK activity by RNA interference, kinase inhibition, and antibody neutralization consistently induced defective larvae with distinct gaps between the exoskeleton and internal tissues. In these abnormal individuals, mitoses were detected to be largely inhibited in the affected regions. These results display the requirement of RSK activity during Artemia development and suggest its role in termination of cell cycle (G(2)/M phase) arrest and promotion of mitogenesis. Our findings may, thus, provide insights into the regulation of cell division during Artemia post-embryonic development and reveal further aspects of RSK functions.