ATF5 regulates β-cell survival during stress

Significance The survival and function of insulin-secreting β cells is critical for the prevention of diabetes. We identify a previously unknown function for activating transcription factor 5 (ATF5) in the apoptotic susceptibility of β cells. ATF5 expression in β cells is stress inducible, and ATF5 deficiency results in a significant increase in β-cell apoptosis in response to stress. Further, eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1), a component of the mammalian target of rapamycin (mTOR) pathway that inhibits protein translation through interaction with EIF4E, is regulated by ATF5 and likely is involved in apoptotic susceptibility through regulation of global translation. Understanding the role of ATF5 deepens our understanding of the complex mechanisms governing β-cell fate decisions, providing a potential pathway for the prevention of diabetes.