Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation

M. Gompel , C. Soulie , I. Ceballos-Picot , L. Meijer (1)

1 MCT - Molécules et cibles thérapeutiques

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.

Mots clés: Antineoplastic Agents/pharmacology Cell Differentiation/drug effects/*physiology Cell Line; Tumor Cell Survival Comparative Study Cyclin-Dependent Kinases/*metabolism Dose-Response Relationship; Drug Enzyme Activation/drug effects Enzyme Inhibitors/chemistry/pharmacology Glycogen Synthase Kinase 3/*metabolism Humans Immunoblotting/methods Neurons/cytology/*enzymology Research Support; Non-U.S. Gov't Teratocarcinoma Time Factors Tretinoin/pharmacology

Domaines: Biochimie [q-bio.BM]

M. Gompel, C. Soulie, I. Ceballos-Picot, L. Meijer. Expression and activity of cyclin-dependent kinases and glycogen synthase kinase-3 during NT2 neuronal differentiation. Neurosignals, 2004, 13, pp.134-143. ⟨hal-00020117⟩