Department of Chemistry and Molecular Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Mol Cell Endocrinol. 2014 Jan 25;382(1):480-487. doi: 10.1016/j.mce.2013.07.027. Epub 2013 Aug 3.
Mammalian oocytes arrest at prophase of meiosis I at around birth and they remain arrested at this stage until puberty when the preovulatory surge of luteinizing hormone (LH) causes ovulation. Prophase I arrest in the immature oocyte results from the maintenance of low activity of maturation promoting factor (MPF), which consists of a catalytic subunit (CDK1) and regulatory subunit (cyclin B1). Phosphorylation-mediated inactivation of CDK1 and constant degradation of cyclin B1 keep MPF activity low during prophase I arrest. LH-mediated signaling manipulates a vast array of molecules to activate CDK1. Active CDK1 not only phosphorylates different meiotic phosphoproteins during the resumption of meiosis but also inhibits their rapid dephosphorylation by inhibiting the activities of CDK1 antagonizing protein phosphatases (PPs). In this way, CDK1 both phosphorylates its substrates and protects them from being dephosphorylated. Accumulating evidence suggests that the net MPF activity that drives the resumption of meiosis in oocytes depends on the activation status of CDK1 antagonizing PPs. This review aims to provide a summary of the current understanding of the signaling pathways involved in regulating MPF activity during prophase I arrest and reentry into meiosis of mammalian oocytes.
哺乳动物卵母细胞在出生时停滞在减数分裂 I 的前期，并在青春期前促黄体激素 (LH) 的促排卵激增之前一直处于停滞状态。未成熟卵母细胞的前期 I 阻滞是由于成熟促进因子 (MPF) 的活性保持较低水平，MPF 由催化亚基 (CDK1) 和调节亚基 (cyclin B1) 组成。CDK1 的磷酸化失活和 cyclin B1 的持续降解在前期 I 阻滞期间使 MPF 活性保持较低水平。LH 介导的信号转导操纵大量分子来激活 CDK1。活性 CDK1 不仅在减数分裂恢复期间磷酸化不同的减数分裂磷酸蛋白，而且通过抑制其拮抗蛋白磷酸酶 (PP) 的活性来抑制其快速去磷酸化，从而保护它们免受去磷酸化。越来越多的证据表明，驱动卵母细胞减数分裂恢复的净 MPF 活性取决于调节 CDK1 拮抗 PP 的激活状态。本综述旨在提供一个当前对调控哺乳动物卵母细胞前期 I 阻滞和重新进入减数分裂过程中 MPF 活性的信号通路的理解的概述。
