TY - JOUR T1 - Cyclin Dependent Kinase Inhibitors and Dominant Negative Cyclin Dependent Kinase 4 and 6 Promote Survival of NGF-Deprived Sympathetic Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8975 LP - 8983 DO - 10.1523/JNEUROSCI.17-23-08975.1997 VL - 17 IS - 23 AU - David S. Park AU - Beth Levine AU - Giovanna Ferrari AU - Lloyd A. Greene Y1 - 1997/12/01 UR - http://www.jneurosci.org/content/17/23/8975.abstract N2 - Neuronal apoptosis plays a critical role in both normal development and disease. However, the precise molecular events controlling neuronal apoptosis are not well understood. Previously, we hypothesized that cell cycle regulatory molecules function in controlling the apoptotic pathways of trophic factor-deprived neurons. To test this hypothesis, we used the RNA alphavirus Sindbis to express three known cyclin dependent kinase inhibitors (CKIs), p16ink4, p21waf/cip, and p27kip1, and dominant negative mutant forms of four known G1 cyclin dependent kinases (CDKs), Cdk2, Cdk3, Cdk4, and Cdk6, in primary cultured rat superior cervical ganglion sympathetic neurons. We demonstrate that expression of each of the CKIs protects the postmitotic cultured neurons from apoptotic death evoked by withdrawal of NGF. In addition, we show that expression of dominant negative forms of Cdk4 or Cdk6, but not Cdk2 or Cdk3, protects NGF-deprived sympathetic neurons from death. Such findings suggest the participation of several CDKs and their cognate cyclins in a neuronal apoptotic pathway. ER -