Maternal Wnt/STOP signaling promotes cell division during early Xenopus embryogenesis

Maternal Wnt/STOP signaling promotes cell division during early Xenopus embryogenesis
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DOI:
10.1073/pnas.1423533112
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发表时间:
2015-05-05
影响因子:
11.1
通讯作者:
Niehrs, Christof
Niehrs, Christof
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Huang, Ya-Lin;Anvarian, Zeinab;Niehrs, Christof

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在非洲爪哇的发育过程中,Wnt信号被认为首先在中期胚泡过渡后发挥作用,通过β-连环蛋白介导的转录来调节轴型模式。在这里,我们报告了Wnt/糖原合成酶激酶3(GSK3)信号在成熟卵母细胞中已经转录后通过Wnt/稳定蛋白(STOP)信号发挥作用。WNT信号在卵母细胞进入减数分裂中期II后被诱导,进入间期后再次减弱。WNT信号抑制GSK3,从而保护成熟卵母细胞中的蛋白质免受泛素化和降解。在蛋白质阵列筛选中,我们鉴定了一组非洲爪哇有丝分裂效应蛋白,它们以依赖于GSK3的方式多泛素化。因此,母体Wnt/Stop信号的抑制,而不是β-连环蛋白信号的抑制,会导致受精后早期卵裂停止。这些结果支持Wnt信号在细胞周期进程中独立于β-catenin的新作用。
During Xenopus development, Wnt signaling is thought to function first after midblastula transition to regulate axial patterning via beta-catenin-mediated transcription. Here, we report that Wnt/glycogen synthase kinase 3 (GSK3) signaling functions posttran-scriptionally 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 beta-catenin signaling, leads to early cleavage arrest after fertilization. The results support a novel role for Wnt signaling in cell cycle progression independent of beta-catenin.