The Unfolded Protein Response (UPR)
Our understanding of the ER stress response has expanded greatly over the last three decades.We now know that accumulation of misfolded proteins in the ER can elicit an array of cellular responses including: (1) reduction or inhibition in the rate of protein synthesis [2]; (2)upregulation of genes that encode for ER chaperones, enzymes, and structural components of the ER, enabling the organelle to process more proteins [3]; and (3) initiation of programmed cell death (apoptosis) if the stress is too severe [2,4]. These UPR cellular responses are downstream from parallel activation of three key ER-transmembrane proteins: IRE1, ATF6, and PERK.