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Transient suppression of nuclear Cdc2 activity in response to ionizing radiation.
- Source :
-
Oncology reports [Oncol Rep] 2008 May; Vol. 19 (5), pp. 1323-9. - Publication Year :
- 2008
-
Abstract
- Suppression of Cdc2 activity is essential for DNA damage-induced G2 arrest. In the present study, we elucidated regulatory mechanism of Cdc2 activity during radiation-induced transient G2 arrest. Exposure of the cells to gamma-radiation (4 Gy) led to a transient increase of cells in G2 at 12 h rather than M phase and then the cells resumed cell cycle progression from the G2 arrest. However, the levels of cyclin B1 and Cdc2 activity were increased in the whole cell extracts at 12 h. Despite cyclin B1 induction and increased level of Cdc2 activity after irradiation the activities in the nuclear fractions were transiently decreased at 12 h and returned to control levels by 24-48 h, demonstrating transient inhibition of nuclear translocation of cyclin B1 in response to radiation. Moreover, inhibitory phosphorylation of the Cdc2 on Tyr15 and the Cdc25C on Ser216 were increased concomitant with transient G2 arrest. The level of phosphorylated Wee1 and its activity were also markedly increased at 12 h after irradiation. In addition, radiation caused nuclear accumulation of p21(CIP1/WAF1) at 12 h, resulting in increased-binding of p21(CIP1/WAF1) to Cdc2. Nuclear p21(CIP1/WAF1) protein level and its binding to Cdc2 gradually returned to control level when the cells resumed cell cycle progression. However, total protein level of p21(CIP1/WAF1) continued to increase until 48 h after irradiation. Collectively, these results indicate that the suppression of nuclear import of cyclin B1, the induction of Wee1 kinase activity, and the transient nuclear accumulation of p21(CIP1/WAF1) may play important roles in the transient cell cycle delay in response to ionizing radiation.
- Subjects :
- Animals
CDC2 Protein Kinase physiology
Cell Cycle
Cell Proliferation
Cyclin B1
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Gamma Rays
Mice
Mitosis
Phosphorylation
Active Transport, Cell Nucleus
CDC2 Protein Kinase biosynthesis
Cell Cycle Proteins biosynthesis
Cell Nucleus metabolism
Cyclin B biosynthesis
Cyclin-Dependent Kinase Inhibitor p21 biosynthesis
Gene Expression Regulation, Neoplastic
Nuclear Proteins biosynthesis
Protein-Tyrosine Kinases biosynthesis
Radiation, Ionizing
Subjects
Details
- Language :
- English
- ISSN :
- 1021-335X
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 18425394