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Cyclic AMP-dependent transcription factor ATF-4 (ATF4) is a basic leucine-zipper (bZip) transcription factor, which regulates amino acid metabolism, DNA damage repair, chromatin remodeling, and apoptosis in response to cellular and ER stress. ATF4 works with various proteins, such as C/EBP homology protein (CHOP), aspargine synthetase (ASNS), and cAMP response element (CRE) among others to mediate cellular stress. ATF4 also regulates glucose homeostasis by suppressing beta-cell proliferation and insulin production. Furthermore, ATF4 targets the histone demethylase JMJD3 to alter chromatin structure and enhance gene transcription in response to amino acid deprivation.