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[Control of cell division in eucaryotes]
1Centre de Recherches sur la Biochimie des Macromolécules, CNRS et INSERM, Montpellier, France.
Abstract:
In eucaryotes, M-phase promoting factor (MPF) triggers meiosis in germ cells and mitosis in somatic cells. MPF is composed of two proteins of which one is homologous with the protein kinase encoded by gene cdc2 of Schizosaccharomyces pombe (p34cdc2) and the other is a cyclin whose concentration oscillates during the cell cycle. Inactivation of p34cdc2 (MPF) requires cyclin degradation, which occurs during the metaphase-anaphase transition of the M-phase. Cyclin degradation is not only associated with cell cycle progression, but is also required for this event. At the G2/M transition, p34cdc2 protein kinase is activated and catalyzes phosphorylation of numerous key proteins, thus enabling cell changes to occur. p34cdc2 undergoes multiple-site phosphorylation in a cell cycle-dependent manner. At onset of mitosis, the protein phosphatase cdc25 catalyzes dephosphorylation of the p34cdc2 kinase at the threonine 14 and tyrosine 15 sites. This event may be the rate-limiting step controlling onset of mitosis in cells of vertebrates. A second protein kinase, encoded by the proto-oncogene c-mos, acts as a cytostatic factor preventing cyclin degradation and keeping unfertilized eggs from progressing beyond the second meiotic metaphase.
Insights
M-phase promoting factor (MPF), comprising p34cdc2 and cyclin, drives cell division. Cyclin degradation is essential for MPF inactivation and cell cycle progression, with cdc25 phosphatase regulating mitosis onset.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- M-phase promoting factor (MPF) regulates meiosis and mitosis in eukaryotes.
- MPF consists of p34cdc2 protein kinase and a cyclin component.
- Cyclin concentration oscillates, controlling cell cycle progression.
Purpose of the Study:
- To elucidate the regulatory mechanisms of MPF activity and cell cycle progression.
- To investigate the role of cyclin degradation in MPF inactivation.
- To understand the function of p34cdc2 phosphorylation and dephosphorylation in mitosis.
Main Methods:
- Analysis of protein kinase and phosphatase activities.
- Investigation of protein-protein interactions (p34cdc2 and cyclin).
- Study of cell cycle-dependent phosphorylation and dephosphorylation events.
Main Results:
- Cyclin degradation is required for MPF inactivation at the metaphase-anaphase transition.
- p34cdc2 kinase is activated at the G2/M transition via phosphorylation.
- Dephosphorylation of p34cdc2 by cdc25 phosphatase at Thr14/Tyr15 is critical for mitosis onset.
- c-mos proto-oncogene kinase acts as a cytostatic factor, inhibiting cyclin degradation and meiotic progression.
Conclusions:
- MPF activity is tightly regulated by cyclin levels and p34cdc2 phosphorylation status.
- Cyclin degradation is a crucial checkpoint for cell cycle progression.
- The cdc25 phosphatase-mediated dephosphorylation of p34cdc2 is a key regulatory step for mitosis.
- The c-mos kinase plays a role in preventing premature cell cycle progression in oocytes.