Inoue Daigo, Ohe Munemichi, Kanemori Yoshinori, Nobui Toshiya, Sagata Noriyuki
Department of Biology, Graduate School of Sciences, Kyushu University, Hakozaki 6-10-1, Fukuoka 812-8581, Japan.
Nature. 2007 Apr 26;446(7139):1100-4. doi: 10.1038/nature05688. Epub 2007 Apr 4.
In vertebrates, unfertilized eggs (or mature oocytes) are arrested at metaphase of meiosis II by a cytoplasmic activity called cytostatic factor (CSF). The classical Mos-MAPK pathway has long been implicated in CSF arrest of vertebrate eggs, but exactly how it exerts CSF activity remains unclear. Recently, Erp1 (also called Emi2), an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) required for degradation of the mitotic regulator cyclin B (ref. 5), has also been shown to be a component of CSF in both Xenopus and mice. Erp1 is destroyed on fertilization or egg activation, like Mos. However, despite these similarities the Mos-MAPK (mitogen-activated protein kinase) pathway and Erp1 are thought to act rather independently in CSF arrest. Here, we show that p90rsk, the kinase immediately downstream from Mos-MAPK, directly targets Erp1 for CSF arrest in Xenopus oocytes. Erp1 is synthesized immediately after meiosis I, and the Mos-MAPK pathway or p90rsk is essential for CSF arrest by Erp1. p90rsk can directly phosphorylate Erp1 on Ser 335/Thr 336 both in vivo and in vitro, and upregulates both Erp1 stability and activity. Erp1 is also present in early embryos, but has little CSF activity owing, at least in part, to the absence of p90rsk activity. These results clarify the direct link of the classical Mos-MAPK pathway to Erp1 in meiotic arrest of vertebrate oocytes.
在脊椎动物中，未受精的卵（或成熟卵母细胞）通过一种称为细胞静止因子（CSF）的细胞质活性停滞在减数分裂II中期。长期以来，经典的Mos-MAPK途径一直被认为与脊椎动物卵的CSF停滞有关，但它究竟如何发挥CSF活性仍不清楚。最近，Erp1（也称为Emi2），一种有丝分裂调节因子细胞周期蛋白B降解所需的后期促进复合物/细胞周期体（APC/C）的抑制剂，在非洲爪蟾和小鼠中也被证明是CSF的一个组成部分。与Mos一样，Erp1在受精或卵激活时被破坏。然而，尽管有这些相似之处，Mos-MAPK（丝裂原活化蛋白激酶）途径和Erp1被认为在CSF停滞中相当独立地发挥作用。在这里，我们表明，Mos-MAPK下游的激酶p90rsk直接靶向Erp1，以在非洲爪蟾卵母细胞中实现CSF停滞。Erp1在减数分裂I后立即合成，Mos-MAPK途径或p90rsk对于Erp1介导的CSF停滞至关重要。p90rsk可以在体内和体外直接磷酸化Erp1的Ser 335/Thr 336位点，并上调Erp1的稳定性和活性。Erp1也存在于早期胚胎中，但由于至少部分缺乏p90rsk活性，其CSF活性较低。这些结果阐明了经典的Mos-MAPK途径与Erp1在脊椎动物卵母细胞减数分裂停滞中的直接联系。
