Cyclin dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF-deprived sympathetic neurons

David S. Park, Beth Levine, Giovanna Ferrari, Lloyd A. Greene

Research output: Contribution to journalArticle

240 Scopus citations

Abstract

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), p16(ink4), p21 (waf/cip), and p27(kip1), 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.

Original languageEnglish (US)
Pages (from-to)8975-8983
Number of pages9
JournalJournal of Neuroscience
Volume17
Issue number23
DOIs
StatePublished - 1997

Keywords

  • Apoptosis
  • CDK
  • Cell cycle
  • Cell death
  • Sindbis
  • Sympathetic neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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