Ectopic expression of p27(Kip1) in oligodendrocyte progenitor cells results in cell-cycle growth arrest Journal Article
| Authors: | Tikoo, R.; Osterhout, D. J.; Casaccia-Bonnefil, P.; Seth, P.; Koff, A.; Chao, M. V. |
| Article Title: | Ectopic expression of p27(Kip1) in oligodendrocyte progenitor cells results in cell-cycle growth arrest |
| Abstract: | Oligodendrocyte differentiation is a complex process believed to be controlled by an intrinsic mechanism associated with cell-cycle arrest. Recently, the cell-cycle inhibitor protein p27(Kip1) has been proposed as a key element in causing growth arrest of oligodendrocyte precursor cells. To investigate the effects of p27 upon oligodendrocyte cell development, we have introduced the p27 cDNA in oligodendrocyte progenitor cells using an adenovirus vector. Progenitor cells normally express low levels of p27. After adenoviral infection and p27 overexpression, progenitor cells were able to undergo cell-cycle arrest, even in the presence of strong mitogens. The effects of p27 were shown to be directly upon cyclin-dependent kinase-2 (CDK2), the protein kinase complex responsible for G1/S transition, as immunodepletion of oligodendrocyte extracts of p27 protein resulted in the activation of CDK2 activity. However, cells that became growth arrested owing to infection with p27 adenovirus did not display conventional oligodendrocyte differentiation markers, such as 04 or 01. Taken together, these data provide mechanistic evidence indicating that p27 is primarily involved in oligodendroglial progenitor proliferation by inhibiting CDK2 activity and inducing oligodendrocyte cell-cycle arrest. |
| Keywords: | immunohistochemistry; protein expression; genetics; nonhuman; cell cycle protein; metabolism; cell cycle proteins; animal tissue; cells, cultured; cell cycle; gene overexpression; protein kinases; cell differentiation; protein serine threonine kinase; physiology; gene transfer; stem cell; blotting, western; biosynthesis; diagnostic agent; cell culture; protein-serine-threonine kinases; cyclin dependent kinase inhibitor 1b; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; rat; western blotting; newborn; stem cells; tumor suppressor protein; cyclin-dependent kinases; cyclin dependent kinase; nerve cell differentiation; protein kinase; cyclin-dependent kinase; antimetabolite; differentiation; adenoviridae; broxuridine; bromodeoxyuridine; growth inhibition; gene transfer techniques; adenovirus; cyclin dependent kinase 2; cyclin-dependent kinase 2; oligodendroglia; cdk2 protein, human; antimetabolites; oligodendrocyte; cdc2-cdc28 kinases; humans; human; priority journal; article; histone h1 kinase |
| Journal Title: | Journal of Neurobiology |
| Volume: | 36 |
| Issue: | 3 |
| ISSN: | 0022-3034 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1998-09-05 |
| Start Page: | 431 |
| End Page: | 440 |
| Language: | English |
| DOI: | 10.1002/(sici)1097-4695(19980905)36:3<431::aid-neu10>3.0.co;2-e |
| PUBMED: | 9733077 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
