Eukaryotic Initiation Factor 2B and Its Role in Alterations in mRNA Translation That Occur Under a Number of Pathophysiological and Physiological Conditions

Abstract

Publisher Summary Eukaryotic initiation factor (eIF)2B is a guanine nucleotide exchange factor (GEF) for a second initiation factor, eIF2. During the initiation of messenger RNA (mRNA) translation, eIF2 binds Guanosine-5'-triphosphate (GTP) and initiator methionyl- transfer RNA (tRNA i ) (met-tRNA i ) and the resulting ternary complex subsequently binds to the 40S ribosomal subunit. Alterations in ternary complex formation due to changes in eIF2B GEF activity not only produce alterations in global rates of protein synthesis but also cause specific changes in the translation of mRNAs encoding certain proteins, such as the transcription factors general control nonrepressed 2 (GCN2) and activating transcription factor 4 (ATF4). Studies have implicated changes in eIF2B GEF activity in alterations in protein synthesis in a number of pathophysiological and physiological conditions, such as diabetes, cancer, sepsis, vanishing white matter disease, and resistance exercise. The chapter discusses the state of knowledge concerning the function of eIF2B and its role in regulating mRNA translation.