INHIBITION OF CYCLIN-DEPENDENT KINASE-ACTIVITY TRIGGERS NEURONAL DIFFERENTIATION OF MOUSE NEUROBLASTOMA-CELLS

Studies on the molecular mechanisms underlying neuronal differentiatio n are frequently performed using cell lines established from neuroblas tomas. In this study we have used mouse N1E-115 neuroblastoma cells th at undergo neuronal differentiation in response to DMSO. During differ entiation, cyclin-dependent kinase (cdk) activities decline and phosph orylation of the retinoblastoma gene product (pRb) is lost, leading to the appearance of a pRb-containing E2F DNA-binding complex. The loss of cdk2 activity is due to a decrease in cdk2 abundance whereas loss o f cdk4 activity is caused by strong association with the cdk inhibitor (CKI) p27(KIP1) and concurrent loss of cdk4 phosphorylation. Moreover , neuronal differentiation can be induced by overexpression of p27(KIF 1) or pRb, suggesting that inhibition of cdk activity leading to loss of pRb phosphorylation, is the major determinant for neuronal differen tiation.