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The Cyclin-Dependent Kinase Inhibitor p21 WAF1 Is Required for Survival of Differentiating Neuroblastoma Cells

1996; Taylor & Francis; Volume: 16; Issue: 4 Linguagem: Inglês

10.1128/mcb.16.4.1335

1098-5549

Wojciech Poluha, Dorota K. Poluha, Baochong B. Chang, Nancy E. Crosbie, Christopher M. Schonhoff, Daniel L. Kilpatrick, Alonzo H. Ross,

Epigenetics and DNA Methylation

We are employing recent advances in the understanding of the cell cycle to study the inverse relationship between proliferation and neuronal differentiation.Nerve growth factor and aphidicolin, an inhibitor of DNA polymerases, synergistically induce neuronal differentiation of SH-SY5Y neuroblastoma cells and the expression of p21 WAF1 , an inhibitor of cyclin-dependent kinases.The differentiated cells continue to express p21 WAF1 , even after removal of aphidicolin from the culture medium.The p21 WAF1 protein coimmunoprecipitates with cyclin E and inhibits cyclin E-associated protein kinase activity.Each of three antisense oligonucleotides complementary to p21 WAF1 mRNA partially blocks expression of p21 WAF1 and promotes programmed cell death.These data indicate that p21 WAF1 expression is required for survival of these differentiating neuroblastoma cells.Thus, the problem of neuronal differentiation can now be understood in the context of negative regulators of the cell cycle.