eIF2dependent

eIF2dependent refers to cellular processes or regulatory mechanisms that rely on the activity of eukaryotic translation initiation factor 2 (eIF2). eIF2 is a crucial protein complex that plays a central role in the initiation of protein synthesis. It binds to GTP and the initiator tRNA (Met-tRNAi) and delivers this ternary complex to the 40S ribosomal subunit, marking the first step in translation.

Regulation of eIF2 activity is a critical control point for protein synthesis and is often linked to cellular stress responses. Under certain stress conditions, such as amino acid starvation, endoplasmic reticulum stress, or viral infection, specific kinases phosphorylate the alpha subunit of eIF2 (eIF2α). This phosphorylation event leads to the formation of a stable complex between eIF2α-GDP and the guanine nucleotide exchange factor eIF2B, sequestering eIF2B and inhibiting the recycling of eIF2-GDP to eIF2-GTP. Consequently, overall protein synthesis is globally attenuated.

This global shutdown of translation, however, is not absolute. The phosphorylation of eIF2α also leads to the preferential translation of certain messenger RNAs (mRNAs) that contain upstream open reading frames (uORFs) in their 5' untranslated regions. These specific mRNAs often encode proteins involved in stress adaptation and survival. Therefore, eIF2dependent pathways are essential for maintaining cellular homeostasis by both reducing general protein synthesis under stress and allowing the synthesis of specific survival factors. The precise mechanisms and downstream consequences of eIF2dependent regulation are areas of ongoing research.