The Role of "Cytostatic Factor (CSF)" in the Control of Oocyte Cell Cycles: A Summary of 20 Years of Study:...

Cytostatic Factor (CSF) is a cytoplasmic factor found in unfertilized eggs of the frog that causes metaphase arrest of cell cycles in the oocyte and zygote. CSF appears in maturing oocyte cytoplasm, but disappears during egg activation. CSF-injected zygotes are arrested at metaphase and show morphology and cellular activities strikingly similar to those of unfertilized eggs. Fresh cytosols extracted from unfertilized eggs contain unstable CSF, called "primary" CSF, which is highly sensitive to Ca ions. Cytosols incubated with Ca ions develop stable CSF, called "secondary" CSF, which is resistant to Ca ions. It has been hypothesized that primary CSF is responsible for the metaphase arrest of meiosis in the unfertilized egg, and its inactivation by a surge of Ca ions during fertilization releases the egg from metaphase arrest. Studies of molecular characteristics of partially purified primary and secondary CSFs suggest that they are both proteins. Recent studies in other laboratories indicate that primary CSF is the c-mos proto-oncogene product. The effect of CSF appears to be primarily stabilization of maturation-promoting factor (MPF), another oocyte cytoplasmic factor, that causes transition of the cell from interphase to metaphase. This paper will summarize the studies on CSF in the author's laboratory over the past 20 years, describe the development of the concept of CSF as a cell cycle regulator, and speculate on the mechanism of its action based on current knowledge.