Phospho-PERK (Thr980) is a phosphorylated form of the protein kinase-like endoplasmic reticulum kinase (PERK), a type I transmembrane protein located in the endoplasmic reticulum (ER). It plays a crucial role in the unfolded protein response (UPR) by activating itself through oligomerization and autophosphorylation at threonine 980 (Thr980) in response to ER stress and the accumulation of misfolded proteins. This phosphorylation enhances PERK's activity, allowing it to phosphorylate eukaryotic translation initiation factor 2 alpha (eIF2伪), which leads to the attenuation of translation initiation and global protein synthesis. This process helps protect cells from the toxic effects of misfolded proteins and maintains cellular homeostasis. Additionally, the activation of PERK is associated with cell cycle arrest due to the loss of cyclin D1 and the regulation of genes involved in metabolism, redox status, and apoptosis.
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