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The mechanism of CSF arrest in vertebrate oocytes
James L Maller1, Markus S Schwab, Stefan D Gross
1The Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, 4200 E. 9th Avenue, Box C236, Denver, CO 80262, USA. jim.maller@uchsc.edu
Abstract:
A cytoplasmic activity in mature oocytes responsible for second meiotic metaphase arrest was identified over 30 years ago in amphibian oocytes. In Xenopus oocytes cytostatic factor (CSF) activity is initiated by the progesterone-dependent synthesis of Mos, a MAPK kinase kinase that activates the MAPK pathway. CSF arrest is mediated by a sole MAPK target, the protein kinase p90(Rsk). Rsk phosphorylates and activates the Bub1 protein kinase, which may cause metaphase arrest due to inhibition of the anaphase-promoting complex (APC) by a conserved mechanism defined genetically in yeast and mammalian cells. CSF arrest in vertebrate oocytes by p90(Rsk) provides a link between the MAPK pathway and the spindle assembly checkpoint in the cell cycle.
Insights
Cytostatic factor (CSF) in Xenopus oocytes arrests meiosis II. This arrest is mediated by Mos and MAPK pathway activation, leading to p90(Rsk) phosphorylating Bub1, which inhibits the anaphase-promoting complex (APC).
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- A cytoplasmic activity, cytostatic factor (CSF), causes metaphase arrest in mature oocytes.
- In Xenopus, CSF is initiated by progesterone, leading to Mos synthesis and MAPK pathway activation.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying CSF-mediated metaphase arrest in Xenopus oocytes.
- To identify the downstream targets of the MAPK pathway involved in cell cycle arrest.
Main Methods:
- Investigated the role of Mos and the MAPK pathway in oocyte maturation.
- Identified and characterized the function of p90(Rsk) as a key MAPK target.
- Examined the interaction between p90(Rsk) and Bub1 protein kinase.
Main Results:
- CSF arrest is dependent on Mos and MAPK pathway activation.
- p90(Rsk) was identified as the sole MAPK target mediating CSF arrest.
- p90(Rsk) phosphorylates and activates Bub1, linking the MAPK pathway to the spindle assembly checkpoint.
Conclusions:
- p90(Rsk) is a crucial mediator of CSF arrest in Xenopus oocytes.
- The findings establish a link between the MAPK pathway and the spindle assembly checkpoint via Bub1.
- This mechanism of metaphase arrest is conserved across vertebrates.