PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis

PC3TIS21/BTG2 is member of a novel family of antiproliferative genes (BTG1, ANA/BTG3, PC3B, TOB, and TOB2) that play a role in cellu- lar di¡erentiation. We have previously shown that PC3TIS21/BTG2 is induced by nerve growth factor (NGF) at the onset of neuronal di¡erentiation in the neural crest-derived PC12 cell line, and is a marker for neuronal birth. We now observe that PC3TIS21/BTG2 ectopically expressed in PC12 cells synergises with NGF, similarly to the cyclin-dependent kinase inhibitor p21, potentiating the induction of the neuronal markers tyrosine hydroxylase and neuro¢lament 160 kDa. Furthermore, PC3TIS21/BTG2 protects from apoptosis elicited by NGF deprivation in terminally di¡erentiated PC12 cultures. Such e¡ects might be a consequence of the arrest of cell cycle exerted by PC3TIS21/BTG2, or expression of a sensitising (neurogenic)propertyofthemolecule.