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.
Highlights
THE JOURNAL OF BIOLOGICAL CHEMISTRY55667–55674, 2004 Printed in U.S.A. Nerve Growth Factor Receptor Signaling Induces Histone Acetyltransferase Domain-dependent Nuclear Translocation of p300/cyclic AMP-responsive element-binding protein (CREB)-binding Protein-associated Factor and hGCN5 Acetyltransferases*
We demonstrate that NGF receptor signaling induces phosphorylation and HAT domain-dependent nuclear translocation of protein-associated factor (PCAF) and hGCN5 acetyltransferases
Immunofluorescence laser confocal microscopy was performed to determine the subcellular distributions of transcriptional coactivators, PCAF and p300, in response to NGF receptor signaling
Summary
55667–55674, 2004 Printed in U.S.A. Nerve Growth Factor Receptor Signaling Induces Histone Acetyltransferase Domain-dependent Nuclear Translocation of p300/CREB-binding Protein-associated Factor and hGCN5 Acetyltransferases*. 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. Neurotrophin stimulation induces p53K320 acetylation by PCAF and transcriptionally activates p53-responsive enhancer elements within the p21WAF/CIP1 promoter associated with G1/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. Our results suggest that signal-dependent HAT trafficking may increase the complexity of neuronal gene regulation and allude to a novel mechanism for ligand/receptor modulation of nuclear PCAF and hGCN5 interactions
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