p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and cell proliferation and survival.
ATF5 has been shown to be a critical regulator of cell proliferation and survival; however, the underlying mechanism remains largely unknown. We demonstrate here that ATF5 interacts with the transcriptional coactivator p300, which acetylates ATF5 at lysine-29 (K29), which in turn enhances the interaction between ATF5 and p300 and binding ... of the ATF5/p300 complex to the ATF5 response element (ARE) region of the Egr-1 promoter. ARE-bound ATF5/p300 acetylates lysine-14 (K14) of nucleosomal histone H3 at both the ARE and serum response element (SRE) of the Egr-1 promoter, which facilitates binding of extracellular signal-regulated kinase (ERK)-phosphorylated Elk-1 to the SRE, activating the Egr-1 promoter. Interference of p300-dependent acetylation of ATF5 or nucleosomal histone H3 or blockade of ERK-dependent Elk-1 phosphorylation abrogates ATF5-dependent Egr-1 activation and cell proliferation and survival. These findings assign a central role for the ATF5/p300 complex in ATF5 function and suggest that coordinated actions by ATF5, p300, Elk-1, and ERK/mitogen-activated protein kinase (MAPK) are essential for ATF5-dependent Egr-1 activation and cell proliferation and survival.
Mesh Terms:
Acetylation, Activating Transcription Factors, Cell Line, Tumor, Cell Proliferation, Cell Survival, DNA-Binding Proteins, E1A-Associated p300 Protein, Early Growth Response Protein 1, Extracellular Signal-Regulated MAP Kinases, HEK293 Cells, Histones, Humans, Promoter Regions, Genetic, RNA Interference, RNA, Small Interfering, Response Elements, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription Factors
Acetylation, Activating Transcription Factors, Cell Line, Tumor, Cell Proliferation, Cell Survival, DNA-Binding Proteins, E1A-Associated p300 Protein, Early Growth Response Protein 1, Extracellular Signal-Regulated MAP Kinases, HEK293 Cells, Histones, Humans, Promoter Regions, Genetic, RNA Interference, RNA, Small Interfering, Response Elements, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription Factors
Mol. Cell. Biol.
Date: Sep. 01, 2011
PubMed ID: 21791614
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