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Maturation-promoting factor and the regulation of the cell cycle
J l Maller1, J Gautier, T A Langan
1Department of Pharmacology, University of Colorado School of Medicine, Denver.
Abstract:
Maturation-promoting factor (MPF) is a cell cycle control element able to cause metaphase when injected into amphibian oocytes or when incubated with nuclei in a cell-free system. Highly purified MPF consists of a complex between a 34K (K = 10(3) Mr) serine/threonine protein kinase, identified as a Xenopus homolog of the cdc2+ gene product, p34cdc2, and a 45K substrate, identified as a Xenopus B-type cyclin. p34cdc2 is also present in purified preparations of chromatin-derived growth-associated histone H1 kinase from Novikoff hepatoma cells. p34cdc2 is active when dephosphorylated and inactive when phosphorylated during oocyte meiotic cell cycles and in mitotic cell cycles following egg activation. Analysis of the substrate specificity of p34cdc2 indicates a consensus sequence for phosphorylation of (K/R)S/TP(X)K/R. Among substrates identified with this consensus are histone H1 and the pp60c-src proto-oncogene, which is known to be activated and phophorylated in mitosis. MPF injection into oocytes activates ribosomal protein S6 kinase II, which is also a lamin kinase. The mechanism of activation is indirect, possibly involving the c-src proto-oncogene. Continued analysis of regulation of MPF activation/inactivation and characterization of substrates for phosphorylation will have important implications for cell cycle and cell growth control.
Insights
Maturation-promoting factor (MPF), a key cell cycle regulator, comprises p34cdc2 kinase and cyclin. Its activity, controlled by phosphorylation, influences cell division and growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Maturation-promoting factor (MPF) is a critical regulator of the cell cycle, inducing metaphase.
- MPF activity is essential for progression through meiosis and mitosis.
Purpose of the Study:
- To characterize the composition and function of Maturation-promoting factor (MPF).
- To investigate the role of p34cdc2 kinase and its substrates in cell cycle control.
Main Methods:
- Purification of MPF from Xenopus oocytes.
- Biochemical analysis of MPF components, including p34cdc2 and cyclin.
- Substrate specificity analysis of p34cdc2 kinase.
Main Results:
- Highly purified MPF contains a complex of p34cdc2 (a serine/threonine kinase) and a B-type cyclin.
- p34cdc2 kinase activity is regulated by phosphorylation, being active when dephosphorylated and inactive when phosphorylated.
- p34cdc2 phosphorylates substrates like histone H1 and the pp60c-src proto-oncogene, with a consensus phosphorylation sequence of (K/R)S/TP(X)K/R.
Conclusions:
- MPF's composition and phosphorylation-dependent activity are central to cell cycle regulation.
- Understanding MPF regulation and its substrates is crucial for comprehending cell cycle and growth control mechanisms.