Changes in cyclin-dependent kinase 2 and p27kip1 accompany glial cell differentiation of central glia-4 cells.
The generation of different glial cell types in the central nervous system depends upon a wide variety of proliferative and differentiative signals. Here we report that changes in the levels of cyclin-dependent kinase 2 (CDK2) and the cell cycle inhibitor p27kip1 accompany the differentiation of central glia-4 (CG-4) progenitor cells to an astrocytic cell phenotype in the presence of fetal calf serum. Although a decrease in CDK2 levels was observed in both oligodendrocyte and astrocyte cells derived from CG-4 cells, a striking increase in the levels of p27 was observed during the differentiation of astrocyte cells. In astrocyte cell extracts, inhibition of CDK2 activity could be overcome with exogenously added cyclin E. Furthermore, depletion of p27 from astrocyte extracts lowered the amount of cyclin E required for CDK2 activation. Taken together, these results suggest that the inhibitory action of p27 upon cyclin E-CDK2 may prevent entry of cells into the S phase and regulate the progression of CG-4 cells toward an astrocytic lineage.
Tikoo
R
R
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA. rtikoo@mail.med.cornell.edu
Casaccia-Bonnefil
P
P
Chao
M V
MV
Koff
A
A
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D025521:Tumor Suppressor Proteins
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases