Nerve growth factor rapidly regulates VGF gene transcription through cycloheximide sensitive and insensitive pathways.

Nerve growth factor (NGF) initiates and maintains a regulatory cascade, involving gene induction, which results in the neuronal differentiation of PC12 cells. The VGF gene encodes one of the most rapidly induced neuronal mRNAs identified in NGF-treated PC12 cells [Science, 229 (1985) 393-395; Mol. Cell Biol., 11 (1991) 2335-2349]. In this communication we show that NGF-treatment for 60-90 min maximally increases VGF gene transcription by 12- to 14-fold. VGF mRNA half-life was found to substantially decrease in PC12 cells treated with NGF for 9-25 h. Partial inhibition of VGF gene transcription and superinduction of cytoplasmic VGF mRNA levels in the presence of both NGF and cycloheximide suggests that the VGF gene may be regulated through multiple pathways, some of which can be activated in the presence of protein synthesis inhibitors as are the immediate early genes, while others require newly synthesized proteins.