What is unfolded protein response signaling?

Unfolded protein response (UPR) signaling is a rapid cell signaling mechanism that allows the rough endoplasmic reticulum (RER) to communicate with the cell nucleus immediately.

UPR signaling is initiated when physiological or pathological factors disrupt protein folding in the lumen of the RER. The accumulation of unfolded or misfolded proteins causes endoplasmic reticulum stress, which triggers the UPR signaling.

Unfolded protein response signaling accomplishes multiple functions in rapid succession. It signals the nucleus to send fewer messenger molecules to the ribosomes for translation, thereby slowing down the rate of protein synthesis. UPR signaling also boosts the ER’s ability to fold proteins properly and destroy unfolded or misfolded proteins.

If the above two steps fail to alleviate ER stress and reduce the protein pile-up, UPR signaling initiates the self-destruction of the affected cells in a process known as apoptosis. Apoptosis or programmed cell death is a last-ditch attempt to minimize the potential damage caused by excessive accumulation of unfolded or misfolded proteins.