Mos positively regulates Xe-Wee1 to lengthen the first mitotic cell cycle of Xenopus

Abstract

Several key developmental events occur in the first mitotic cell cycle of Xenopus; consequently this cycle has two gap phases and is ~60-75 min in length. In contrast, embryonic cycles 2-12 consist only of S and M phases and are 30 min in length. Xe-Weel and Mos are translated and degraded in a developmentally regulated manner. Significantly, both proteins are present in the first cell cycle. We showed previously that the expression of nondegradable Mos, during early interphase, delays the onset of M phase in the early embryonic cell cycles. Here we report that Xe-Weel is required for the Mos-mediated M-phase delay. We find that Xe-Weel tyrosine autophosphorylation positively regulates Xe-Weel and is only detected in the first 30 rain of the first cell cycle. The level and duration of Xe-Weel tyrosine phosphorylation is elevated significantly when the first cell cycle is elongated with nondegradable Mos. Importantly, we show that the tyrosine phosphorylation of Xe-Wee1 is required for the Mos-mediated M-phase delay. These findings indicate that Mos positively regulates Xe-Weel to generate the G1 phase in the first cell cycle and establish a direct link between the MAPK signal transduction pathway and Wee1 in vertebrates.