[Prevention of cyclin D1 nuclear localization in terminally differentiated neurons].
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 p21Cip1 and p27Kip1. Although forced expression of p 21 caused cyclin D 1 nuclear accumulation, the inhibition of its nuclear export by inhibiting GSK-3 beta 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.
Sumrejkanchanakij
Piyamas
P
Section of Craniofacial Molecular Embryology, Department of Maxillofacial Biology, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University.
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D019938:Cyclin D1 / Q000378:metabolism* / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport
D018797:Cell Cycle Proteins; D019938:Cyclin D1