p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and cell proliferation and survival

David X. Liu, Dongmeng Qian, Bin Wang, Jin Ming Yang, Zhimin Lu

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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 signalregulated 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.

Original languageEnglish (US)
Pages (from-to)3906-3916
Number of pages11
JournalMolecular and cellular biology
Volume31
Issue number18
DOIs
StatePublished - Sep 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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