Nerve Growth Factor Receptor Signaling Induces Histone Acetyltransferase Domain-dependent Nuclear Translocation of p300/CREB-binding Protein-associated Factor and hGCN5 Acetyltransferases

Abstract

The transcriptional coactivators, p300/CREB-binding protein-associated factor (PCAF) and hGCN5, are recruited to chromatin-remodeling complexes on enhancers of various gene promoters in response to growth factor stimulation. However, the molecular mechanisms by which surface receptor signals modulate the assembly of nuclear transcription complexes are not fully understood. Here we report that nerve growth factor receptor signaling induces nuclear translocation of PCAF and hGCN5 dependent upon the phosphorylation of Ser and Thr residues within their histone acetyltransferase domains, which requires activation of PI3K, Rsk2(pp90), and MSK-1. Neurotrophin stimulation induces p53(K320) acetylation by PCAF and transcriptionally activates p53-responsive enhancer elements within the p21(WAF/CIP1) promoter associated with G(1)/S arrest during neuronal differentiation. Most importantly, these findings represent the first evidence for signal-dependent nuclear translocation of PCAF and hGCN5 acetyltransferases and allude to a novel mechanism for ligand/receptor modulation of nuclear chromatin-remodeling complexes in neurons.