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mos proto-oncogene function
G F Vande Woude1, R Buccione, I Daar
1BRI-Basic Research Program, NCI-Frederick Cancer Research Facility, MD 21701.
Abstract:
Maturation promoting factor (MPF) is a cytoplasmic activity that causes oocytes arrested in prophase to resume meiosis. An inactive form of MPF termed pre-MPF exists in fully grown oocytes. In Xenopus oocytes, progesterone induces maturation and pre-MPF activation. These early maturation events require protein synthesis. We have shown that p39mos synthesis is rapidly induced in progesterone-treated Xenopus oocytes during the protein synthesis sensitive period and prior to activation of pre-MPF or germinal vesicle breakdown (GVBD). p39mos may qualify, therefore, as an 'initiator' of maturation. Mouse oocytes undergoing meiotic maturation also express p39mos. Microinjection of antisense mos oligodeoxynucleotides into fully grown mouse and Xenopus oocytes results in the block of meiotic maturation. In Xenopus, antisense-injected oocytes not only lack p39mos, but also lack MPF and fail to undergo GVBD. In the mouse, the microinjected oocytes progress through GVBD, but fail to produce the first polar body; cytogenetic analysis shows they are arrested at the bivalent chromosome stage of metaphase I. This and additional studies with Xenopus oocytes indicate that p39mos is also required throughout maturation. We have shown that p39mos is indistinguishable from the protein product constitutively expressed in NIH/3T3 cells transformed with activated c-mos. It is likely that its activity as a transforming gene may be due to activation of pre-MPF activities in interphase in the somatic cell cycle.
Insights
p39mos protein initiates oocyte maturation by inducing maturation promoting factor (MPF) activation. Blocking p39mos synthesis halts meiosis in Xenopus and mouse oocytes, demonstrating its essential role throughout maturation.
Area of Science:
- Cellular and Molecular Biology
- Developmental Biology
- Reproductive Biology
Background:
- Oocyte maturation involves resuming meiosis, regulated by Maturation Promoting Factor (MPF).
- Progesterone triggers MPF activation and maturation in Xenopus oocytes, requiring protein synthesis.
- An inactive MPF form, pre-MPF, is present in fully grown oocytes.
Purpose of the Study:
- To investigate the role of p39mos in initiating and regulating oocyte meiotic maturation.
- To determine if p39mos is essential for MPF activation and germinal vesicle breakdown (GVBD).
- To assess the function of p39mos throughout the entire maturation process in both Xenopus and mouse oocytes.
Main Methods:
- Studied p39mos synthesis in progesterone-treated Xenopus oocytes.
- Utilized antisense mos oligodeoxynucleotides microinjection in Xenopus and mouse oocytes.
- Analyzed oocyte maturation progression, MPF activity, GVBD, and chromosome behavior.
Main Results:
- p39mos synthesis is rapidly induced before MPF activation and GVBD in Xenopus oocytes.
- Antisense inhibition of p39mos blocked maturation in both Xenopus (no MPF/GVBD) and mouse (arrested at metaphase I).
- p39mos is required throughout oocyte maturation, not just for initiation.
Conclusions:
- p39mos acts as an initiator of oocyte maturation and is essential throughout the process.
- p39mos likely activates pre-MPF, playing a critical role in meiotic resumption.
- The findings suggest p39mos's conserved function in vertebrate oocyte maturation.