title: Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells.
abstract: The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16(INK4a), a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.
authors.affiliation: Section of Molecular Embryology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
authors.forename: Piyamas
authors.initials: P
authors.lastname: Sumrejkanchanakij
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Eto
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D013347:Subcellular Fractions / Q000378:metabolism / Q000473:pathology
chemical_list: D019938:Cyclin D1