title: p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and cell proliferation and survival.
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 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.
authors.affiliation: Departments of Neural and Behavioural Sciences, Penn State University College of Medicine, Hershey, PA 17033, USA. dliu@psu.edu
authors.forename: David X
authors.initials: DX
authors.lastname: Liu
authors.forename: Dongmeng
authors.initials: D
authors.lastname: Qian
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000107:Acetylation; D051696:Activating Transcription Factors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D020218:Response Elements; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C507532:ATF5 protein, human; D051696:Activating Transcription Factors; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D006657:Histones; D034741:RNA, Small Interfering; C502774:SRE protein, human; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases