Transcriptional repression of ATF4 gene by CCAAT/enhancer-binding protein β (C/EBPβ) differentially regulates integrated stress response.

The Journal of Biological Chemistry
Souvik DeyR C Wek

Abstract

Different environmental stresses induce the phosphorylation of eIF2 (eIF2∼P), repressing global protein synthesis coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of genes involved in metabolism and nutrient uptake, antioxidation, and regulation of apoptosis. Because ATF4 is a common downstream target that integrates signaling from different eIF2 kinases and their respective stress signals, the eIF2∼P/ATF4 pathway is collectively referred to as the integrated stress response. Although eIF2∼P elicits translational control in response to many different stresses, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2∼P. The rationale for this discordant induction of ATF4 expression and eIF2∼P in response to UV irradiation is that transcription of ATF4 is repressed, and therefore ATF4 mRNA is not available for preferential translation. In this study, we show that C/EBPβ is a transcriptional repressor of ATF4 during UV stress. C/EBPβ binds to critical elements in the ATF4 promoter, resulting in its transcriptional repression. Expression of C/EBPβ increases in response to UV stress, and the liver-enriched inhibitory protein (LIP) i...Continue Reading

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Citations

Feb 22, 2014·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Akihito HaradaYasuyuki Ohkawa
Nov 5, 2014·The Journal of Clinical Investigation·Alessia PerinoKristina Schoonjans
Nov 10, 2014·Molecular Neurobiology·Na WeiDan Liu
Oct 7, 2016·Archives of Toxicology·Hsueh-Chun WangShau-Ku Huang
Apr 6, 2017·Journal of Zhejiang University. Science. B·Ying-Shan ZhouWei-Huan Fang
May 22, 2017·The Journal of Investigative Dermatology·Ann E CollierDan F Spandau
Feb 15, 2018·Cold Spring Harbor Perspectives in Biology·Ronald C Wek
Sep 16, 2016·EMBO Reports·Karolina Pakos-ZebruckaAdrienne M Gorman
Jul 1, 2016·The Journal of Biological Chemistry·Sara K Young, Ronald C Wek
Sep 25, 2012·Molecular and Cellular Biochemistry·Huifang ZhuYingxiong Wang
Nov 23, 2017·Frontiers in Molecular Neuroscience·Mikaela M CederRobert Fredriksson
Feb 19, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Daniela Correia da SilvaDavid M Pereira
May 28, 2021·Science Advances·Sophie KasparAleksandra Trifunovic

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