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Mos positively regulates Xe-Wee1 to lengthen the first mitotic cell cycle of Xenopus
M S Murakami1, T D Copeland, G F Vande Woude
1Advanced Bioscience Laboratories (ABL)-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 USA.
Abstract:
Several key developmental events occur in the first mitotic cell cycle of Xenopus; consequently this cycle has two gap phases and is approximately 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-Wee1 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-Wee1 is required for the Mos-mediated M-phase delay. We find that Xe-Wee1 tyrosine autophosphorylation positively regulates Xe-Wee1 and is only detected in the first 30 min of the first cell cycle. The level and duration of Xe-Wee1 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-Wee1 to generate the G2 phase in the first cell cycle and establish a direct link between the MAPK signal transduction pathway and Wee1 in vertebrates.
Insights
Mos protein positively regulates Xe-Wee1, a key factor in cell cycle control. This interaction is crucial for establishing the G2 phase during the first cell cycle in Xenopus embryos, linking MAPK signaling to Wee1 function.
Area of Science:
- Developmental Biology
- Cell Cycle Regulation
- Molecular Biology
Background:
- The first mitotic cell cycle in Xenopus is unique, featuring two gap phases (G1 and G2) and lasting 60-75 minutes.
- Subsequent embryonic cell cycles (2-12) are shorter, comprising only S and M phases.
- Key proteins Xe-Wee1 and Mos are developmentally regulated and present during the first cell cycle.
Purpose of the Study:
- To investigate the role of Xe-Wee1 in the Mos-mediated delay of M phase onset.
- To elucidate the regulatory mechanism of Xe-Wee1 activity during the first cell cycle.
- To establish a link between the MAPK pathway and Wee1 in vertebrate development.
Main Methods:
- Expression of nondegradable Mos in early Xenopus embryos.
- Analysis of Xe-Wee1 protein levels and tyrosine phosphorylation.
- Investigating the requirement of Xe-Wee1 tyrosine phosphorylation for Mos-mediated M-phase delay.
Main Results:
- Nondegradable Mos expression delays M phase onset in early embryonic cell cycles.
- Xe-Wee1 tyrosine autophosphorylation positively regulates Xe-Wee1 activity, occurring in the first 30 minutes of the cell cycle.
- Elevated Xe-Wee1 tyrosine phosphorylation levels and duration were observed when the first cell cycle was extended by nondegradable Mos.
- Tyrosine phosphorylation of Xe-Wee1 was essential for the Mos-mediated M-phase delay.
Conclusions:
- Mos positively regulates Xe-Wee1, which is critical for generating the G2 phase in the first Xenopus cell cycle.
- This study establishes a direct connection between the MAPK signal transduction pathway and Wee1 in vertebrates.
- Understanding this interaction provides insights into the precise control of early embryonic development.