XGef mediates early CPEB phosphorylation during Xenopus oocyte meiotic maturation.
XGef mediates early CPEB phosphorylation during Xenopus oocyte meiotic maturation.
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DOI：
10.1091/mbc.e04-07-0585
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发表时间：
2005-03
影响因子：
3.3
通讯作者：
Susana E Martínez;Lei Yuan;C. Lacza;Heather Ransom;G. Mahon;I. Whitehead;L. Hake
中科院分区：
文献类型：
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作者：
Susana E Martínez;Lei Yuan;C. Lacza;Heather Ransom;G. Mahon;I. Whitehead;L. Hake
多聚腺苷酸化诱导的翻译是后生动物发育过程中的一种重要调控机制。在非洲爪蟾卵母细胞减数分裂进程中，多聚腺苷酸化诱导的翻译受磷酸化激活的CPEB调节。XGef是一种鸟嘌呤交换因子，是一种与CPEB相互作用的蛋白质，参与孕酮刺激的卵母细胞成熟的早期步骤。我们发现XGef通过直接影响CPEB功能来影响早期卵母细胞成熟。XGef和CPEB在卵子发生和卵母细胞成熟过程中相互作用，并存在于c-mos信使核糖核蛋白（mRNP）中。两种蛋白质在体外也直接相互作用。XGef过表达增加了卵母细胞成熟早期CPEB磷酸化的水平，这与Mos蛋白积累增加和减数分裂恢复加速直接相关。为了发挥这种作用，XGef必须保留鸟嘌呤交换活性和与CPEB的相互作用。XGef的鸟嘌呤交换缺陷型的过表达，其与CPEB相互作用，不增强早期CPEB磷酸化。XGef的一个版本的过表达，显着减少与CPEB的相互作用，但保留鸟嘌呤交换活性，降低早期CPEB磷酸化和延迟卵母细胞成熟。将XGef抗体注射到卵母细胞中阻断了孕酮诱导的卵母细胞成熟和早期CPEB磷酸化。这些发现表明XGef参与了早期CPEB激活，并在此过程中涉及GT3信号传导。
Polyadenylation-induced translation is an important regulatory mechanism during metazoan development. During Xenopus oocyte meiotic progression, polyadenylation-induced translation is regulated by CPEB, which is activated by phosphorylation. XGef, a guanine exchange factor, is a CPEB-interacting protein involved in the early steps of progesterone-stimulated oocyte maturation. We find that XGef influences early oocyte maturation by directly influencing CPEB function. XGef and CPEB interact during oogenesis and oocyte maturation and are present in a c-mos messenger ribonucleoprotein (mRNP). Both proteins also interact directly in vitro. XGef overexpression increases the level of CPEB phosphorylated early during oocyte maturation, and this directly correlates with increased Mos protein accumulation and acceleration of meiotic resumption. To exert this effect, XGef must retain guanine exchange activity and the interaction with CPEB. Overexpression of a guanine exchange deficient version of XGef, which interacts with CPEB, does not enhance early CPEB phosphorylation. Overexpression of a version of XGef that has significantly reduced interaction with CPEB, but retains guanine exchange activity, decreases early CPEB phosphorylation and delays oocyte maturation. Injection of XGef antibodies into oocytes blocks progesterone-induced oocyte maturation and early CPEB phosphorylation. These findings indicate that XGef is involved in early CPEB activation and implicate GTPase signaling in this process.