Druggable sensors of the unfolded protein response

The unfolded protein response

Where does the UPR function? Between the endoplasmic reticulum (ER) and the nucleus of eukaryotic cells. All secreted proteins and proteins that reside in secretory compartments translocate as nascent peptide chains into the ER, where they may undergo folding, modification and assembly before assuming their functional conformations. The ER maintains a specialized oxidizing environment to aid ch...

The unfolded protein response.

The endoplasmic reticulum (ER) is a principal site for folding and maturation of transmembrane, secretory and ERresident proteins. Perturbations that alter ER homeostasis can lead to accumulation of unfolded proteins (UPs), which is a threat to all living cells. To cope with the stress, cells activate an intracellular signaling pathway – the unfolded protein response (UPR). The UPR is an integr...

Unfolded protein response to autophagy as a promising druggable target for anticancer therapy

The endoplasmic reticulum (ER) is responsible for protein processing. In rapidly proliferating tumor cells, the ER tends to be overloaded with unfolded and misfolded proteins due to high metabolic demand. With the limited protein-folding capacity of the ER, tumor cells often suffer from more ER stress than do normal cells. Thus, cellular stress responses to cope with ER stress, such as the unfo...

SnapShot: The Unfolded Protein Response

Unpacking the Unfolded Protein Response

This year, the Albert Lasker Basic Medical Research Award will be shared by Peter Walter and Kazutoshi Mori for discoveries revealing the molecular mechanism of the unfolded protein response, an intracellular quality control system that detects harmful misfolded proteins in the endoplasmic reticulum and then signals the nucleus to carry out corrective measures.