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EIF2A

eIF2alpha - a regulator of global translation in response to cellular stress

Eukaryotic initiation factor 2 (eIF2) regulates global protein translation by binding to Met-tRNA and the 40S ribosome to form the pre-initiation complex. eIF2 is a heterotrimer consisting of alpha, beta, and gamma subunits. The 36kDA eIF2α subunit serves a key regulatory role. Phosphorylation of the serine residue at position 51 is able to block the formation of the pre-initiation complex and halt global protein translation. This regulatory mechanism allows cells to respond and adapt to diverse stresses such as nutrient deficiencies, viral infection, or general ER-stress.

PKR - Mediating cellular stress responses through multiple signaling pathways

Protein kinase R (PKR) is an intracellular stress-sensing protein that is able to detect and respond to viral infections. While PKR is able to sense and respond to a variety of signals, dsRNA is a well-characterized ligand. dsRNA produced during viral replication binds to PKR and induces a conformational change, dimerization, and exposure of the catalytic autophosphorylation site (1). Once in this active form PKR is able to phosphorylate substrates to regulate cell growth and stress responses.