Two adjacent promoter elements mediate nerve growth factor activation of the c-fos gene and bind distinct nuclear complexes

Abstract

Protooncogene fos is rapidly and transiently induced by nerve growth factor (NGF) in rat pheochromocytoma PC12 cells. Two adjacent promoter elements have been identified to mediate the NGF response. One element colocalizes with the serum response element (SRE) centered at position -308, previously shown to confer inducibility by serum, phorbol 12-myristate 13-acetate, and epidermal growth factor, whereas the other element, termed SRE-2, maps approximately 20 base pairs downstream of the SRE and contains several sequence repeats. This element also confers serum responsiveness. Gel mobility shift assays have demonstrated that there are specific nucleoprotein complexes associated with each element and that these exist in the cell prior to NGF induction. The NGF response is independent of the cAMP-regulatory element(s) and does not require cAMP-dependent protein kinase II, as induction by NGF is retained in the mutant PC12 cell line A126-1B2. Finally, the human heat shock HSP70 promoter is also transcriptionally activated by NGF and appears to bind the same nuclear complex as the SRE-2 element of the c-fos promoter.