終末分化した神経細胞におけるサイクリンD1の核移行抑制
2003 年 70 巻 2 号 p. 131-139
詳細
2003 年 70 巻 2 号 p. 131-139
Terminally differentiated neurons irreversibly withdraw from the cell cycle. The mechanisms governing the activity of cyclin D 1, a key regulator of the cell cycle, during neuronal cell cycle withdrawal are not fully understood. This study shows that cyclin D 1 became predominantly cytoplasmic in differentiated cortical neurons. Cytoplasmic cyclin D 1 assembled with cyclin dependent kinase 4 (CDK 4), and the CDK inhibitors p 21Cip1 and p 27Kip1. Although forced expression of p 21 caused cyclin D 1 nuclear accumulation, the inhibition of its nuclear export by inhibiting GSK-3 β activity had no effect. Furthermore, ectopically expressed cyclin D 1 entered the nucleus of proliferating nervous, but not that of differentiated neurons, whereas ectopic cyclin D 1 in quiescent fibroblasts accumulated in the nucleus and induced cell cycle progression. These results indicate that cyclin D 1 nuclear localization is tightly inhibited in terminally differentiated neurons, and suggest that the regulation of its nuclear import plays a role in neuronal cell cycle withdrawal.
