Involvement Of Polo-like Kinase1(Plk1)in Mitotic Arrest By Inhibition Of The MEK-ERK-RSK1Cascade

Cell division is the basis of organism growth and reproduction, controlled through co-operation of different kinases. Once out of control, this process will lead to the production of cell mass, and in severe cases can cause tumors or cancers. Of these, polo-like kinase1(Plk1) and p90ribosomal S6kinase1(RSK1) play key roles. Plk1is a widespread serine/threonine protein kinases in eukaryotic, its structure and function in evolution are very conservative. It acts as a G2/M trigger and its function involves the maturity of the centrosome, spindle assembly. So Plk1has the role in initialing cell division. RSK1is able to regulate transcription through regulating the expression of many genes, and activating a series of growth-associated proteins such as eEF2kinase, elF4B, etc., thereby promoting G1phase forward. Although previous reports show that Plk1is suppressed by RSK1during meiosis in Xenopus oocytes, it is still not clear whether this is the case during mitosis, or whether Plk1counteracts the effects of RSK1. Few animal models are available for the study of controlled and transient cell cycle arrest. Here we show that encysted embryos (cysts) of the primitive crustacean, Artemia, are ideal for such research since they undergo complete cell cycle arrest when they enter diapause (a state of obligate dormancy). We found that Plk1suppressed the activity of RSK1during embryonic mitosis and that Plk1was inhibited during embryonic diapause and mitotic arrest. And by apoptosis detection method, we found that the degree of apoptosis induced by Plk1and RSK1double interference was more severe than single interference. This showed that RSK1activated in this process is not caused by the apoptotic response. Besides, during the oocyte maturation period, the Plk1and RSK1activation levels in oviparous Artemia were lower than ovoviviparous Artemia, and in the diapause embryos, the activity of Plk1and RSK1was suppressed. This indicated that these two signaling pathways were involved in the formation of Artemia diapause embryos. In addition, studies on HeLa cells using Plk1siRNA interference and overexpression showed that phosphorylation of RSK1increased upon interference and decreased after overexpression, suggesting that Plk1inhibits RSK1. Taken together, these findings provide insights into the regulation of Plk1during cell division and Artemia diapause cyst formation, and the correlation between the activity of Plk1and RSK1.