Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation.
In the presence of retinoic acid undifferentiated NT2 cells turn into terminally differentiated hNT (or NT2N) neurons within 5 weeks. We have used this in vitro cellular model to investigate the changes in expression and activity of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) during this neuronal differentiation process. We here show that CDK1/2 protein level and kinase activity sharply decrease during the NT2-->hNT transition. In contrast, the activity of CDK5/p35 dramatically increases, probably as a result of an enhanced expression of p35 in a stable CDK5 level background. GSK-3 activity increases modestly during the differentiation of hNT cells, and this event correlates with enhanced expression of each of the three GSK-3 isoforms. Pharmacological inhibitors of CDKs and GSK-3 lead to a dose-dependent decrease in cell viability.
Gompel
Marie
M
CNRS, Cell Cycle Group, Station Biologique, Roscoff, France.
Soulié
Cathia
C
Ceballos-Picot
Irène
I
Meijer
Laurent
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D018243:Teratocarcinoma; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014212:Tretinoin; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3