Huang Ya-Lin, Anvarian Zeinab, Döderlein Gabriele, Acebron Sergio P, Niehrs Christof
Division of Molecular Embryology, German Cancer Research Center-Zentrum für Molekulare Biologie der Universität Heidelberg (DKFZ-ZMBH) Alliance, D-69120 Heidelberg, Germany; and.
Division of Molecular Embryology, German Cancer Research Center-Zentrum für Molekulare Biologie der Universität Heidelberg (DKFZ-ZMBH) Alliance, D-69120 Heidelberg, Germany; and
Proc Natl Acad Sci U S A. 2015 May 5;112(18):5732-7. doi: 10.1073/pnas.1423533112. Epub 2015 Apr 21.
During Xenopus development, Wnt signaling is thought to function first after midblastula transition to regulate axial patterning via β-catenin-mediated transcription. Here, we report that Wnt/glycogen synthase kinase 3 (GSK3) signaling functions posttranscriptionally already in mature oocytes via Wnt/stabilization of proteins (STOP) signaling. Wnt signaling is induced in oocytes after their entry into meiotic metaphase II and declines again upon exit into interphase. Wnt signaling inhibits Gsk3 and thereby protects proteins from polyubiquitination and degradation in mature oocytes. In a protein array screen, we identify a cluster of mitotic effector proteins that are polyubiquitinated in a Gsk3-dependent manner in Xenopus. Consequently inhibition of maternal Wnt/STOP signaling, but not β-catenin signaling, leads to early cleavage arrest after fertilization. The results support a novel role for Wnt signaling in cell cycle progression independent of β-catenin.
在非洲爪蟾发育过程中，Wnt信号通路被认为在囊胚中期转换后首次发挥作用，通过β-连环蛋白介导的转录来调节轴向模式形成。在此，我们报告Wnt/糖原合酶激酶3（GSK3）信号通路在成熟卵母细胞中已经通过Wnt/蛋白质稳定化（STOP）信号通路在转录后发挥作用。卵母细胞进入减数分裂中期II后诱导Wnt信号通路，退出到间期时该信号通路再次下降。Wnt信号通路抑制Gsk3，从而保护成熟卵母细胞中的蛋白质不被多聚泛素化和降解。在蛋白质阵列筛选中，我们鉴定出一组有丝分裂效应蛋白，它们在非洲爪蟾中以Gsk3依赖的方式被多聚泛素化。因此，抑制母体Wnt/STOP信号通路而非β-连环蛋白信号通路会导致受精后早期卵裂停滞。这些结果支持了Wnt信号通路在独立于β-连环蛋白的细胞周期进程中的新作用。
