Progesterone and insulin stimulation of CPEB dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3
Progesterone and insulin stimulation of CPEB dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3
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DOI：
10.1101/gad.1136004
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发表时间：
2004-01-01
影响因子：
10.5
通讯作者：
Richter, JD
中科院分区：
文献类型：
--
作者：
Sarkissian, M;Mendez, R;Richter, JD
黄体酮刺激非洲爪蟾卵母细胞成熟需要细胞质多聚腺苷酸化诱导的 mos 和细胞周期蛋白 B mRNA 的翻译。驱动聚腺苷酸化的一种顺式元件是 CPE，它与蛋白质 CPEB 结合。 Aurora A (Eg2) 催化的 CPEB 丝氨酸 174 磷酸化会刺激多聚腺苷酸化，这种磷酸化在卵母细胞接触孕酮后不久就会发生。在这里，我们发现胰岛素还刺激 Aurora A 催化的 CPEB S174 磷酸化、细胞质聚腺苷酸化、翻译和卵母细胞成熟。然而，这些胰岛素诱导的事件由 PI3 激酶和 PKC-zeta 独特控制，它们作用于 Aurora A 的上游。孕酮和胰岛素信号传导途径的交叉发生在糖原合酶激酶 3 (GSK-3) 处，糖原合酶激酶 3 (GSK-3) 调节 Aurora A 的活性。GSK-3 和 Aurora A 在体内相互作用，过度表达的 GSK-3 会抑制 Aurora A 催化的 CPEB 磷酸化。在体外，GSK-3 在 S290/291 上磷酸化 Aurora A，其结果是丝氨酸 349 的自磷酸化。GSK-3 磷酸化 Aurora A 或具有 S290/291D 或 S349D 突变的 Aurora A 蛋白，磷酸化 CPEB 的能力降低或没有。相反，具有 S290/291A 或 S349A 突变的 Aurora A 蛋白具有组成型活性。这些结果表明孕酮和胰岛素通过抑制 GSK-3 来刺激成熟，从而允许 Aurora A 激活和 CPEB 介导的翻译。
Progesterone stimulation of Xenopus oocyte maturation requires the cytoplasmic polyadenylation-induced translation of mos and cyclin B mRNAs. One cis element that drives polyadenylation is the CPE, which is bound by the protein CPEB. Polyadenylation is stimulated by Aurora A (Eg2)-catalyzed CPEB serine 174 phosphorylation, which occurs soon after oocytes are exposed to progesterone. Here, we show that insulin also stimulates Aurora A-catalyzed CPEB S174 phosphorylation, cytoplasmic polyadenylation, translation, and oocyte maturation. However, these insulin-induced events are uniquely controlled by PI3 kinase and PKC-zeta, which act upstream of Aurora A. The intersection of the progesterone and insulin signaling pathways occurs at glycogen synthase kinase 3 (GSK-3), which regulates the activity of Aurora A. GSK-3 and Aurora A interact in vivo, and overexpressed GSK-3 inhibits Aurora A-catalyzed CPEB phosphorylation. In vitro, GSK-3 phosphorylates Aurora A on S290/291, the result of which is an autophosphorylation of serine 349. GSK-3 phosphorylated Aurora A, or Aurora A proteins with S290/291D or S349D mutations, have reduced or no capacity to phosphorylate CPEB. Conversely, Aurora A proteins with S290/291A or S349A mutations are constitutively active. These results suggest that the progesterone and insulin stimulate maturation by inhibiting GSK-3, which allows Aurora A activation and CPEB-mediated translation.