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Differential occurrence of CSF-like activity and transforming activity of Mos during the cell cycle in fibroblasts
K Okazaki1, M Nishizawa, N Furuno
1Division of Molecular Genetics, Kurume University, Fukuoka, Japan.
Abstract:
The Xenopus c-mos proto-oncogene product, Mosxe, possesses cytostatic factor (CSF) activity to arrest maturing oocytes in metaphase II and has weak transforming activity in mouse NIH3T3 cells. We show that Mosxe mutants bearing 'stabilizing' penultimate N-terminal amino acids are strongly transforming and can retard progression through the G2-M phases in Mosxe-transformed cells, probably via their CSF activity. On the other hand, a cyclin-Mosxe fusion protein, which undergoes abrupt degradation at the end of mitosis and is restored to its normal levels only after the G1 phase, transforms cells much less efficiently than a mutated cyclin-Mosxe fusion protein that is stable during M-G1 transition. Moreover, in low-serum medium, cells transformed by the unstable cyclin-Mosxe require a long period to enter the S phase, in contrast with the rapid entry into the S phase of cells transformed by the stable cyclin-Mosxe. These results provide strong evidence that unlike the physiological CSF activity, the transforming activity of Mos is exerted in the G1 phase of the cell cycle.
Insights
The Xenopus c-mos proto-oncogene (Mosxe) arrests oocytes via cytostatic factor (CSF) activity. Its transforming activity, however, occurs in the G1 phase, distinct from its CSF role.
Area of Science:
- Molecular Biology
- Cell Cycle Regulation
- Oncogenesis
Background:
- The Xenopus c-mos proto-oncogene product, Mosxe, is known for its cytostatic factor (CSF) activity, arresting oocytes in metaphase II.
- Mosxe also exhibits weak transforming activity in NIH3T3 cells, suggesting a role beyond oocyte maturation.
Purpose of the Study:
- To investigate the relationship between Mosxe's cytostatic factor (CSF) activity and its transforming potential.
- To determine the specific phase of the cell cycle at which Mosxe exerts its transforming activity.
Main Methods:
- Creation and analysis of Mosxe mutants with altered N-terminal amino acids to assess transforming activity.
- Construction and study of cyclin-Mosxe fusion proteins with varying stability during the M-G1 transition.
- Observation of cell cycle progression (G2-M, G1, S phase) in transformed NIH3T3 cells under different serum conditions.
Main Results:
- Mosxe mutants with stabilized penultimate N-terminal amino acids showed strong transforming activity and G2-M phase retardation, likely via CSF activity.
- A stable cyclin-Mosxe fusion protein transformed cells more efficiently than an unstable one.
- Cells transformed by unstable cyclin-Mosxe exhibited delayed S phase entry in low serum, unlike cells with stable cyclin-Mosxe.
Conclusions:
- The transforming activity of Mosxe is distinct from its physiological CSF activity.
- Mosxe's transforming activity is primarily exerted during the G1 phase of the cell cycle.
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