The unfolded protein response: an intracellular signalling pathway with many surprising features.

The unfolded protein response (UPR) is an intracellular signalling pathway–originating in the endoplasmic reticulum (ER) and leading to the cell nucleus–that controls transcription of genes encoding ER-resident proteins. Recent developments in this field show that this pathway utilizes unique regulatory mechanisms, including translational attenuation and a regulated mRNA splicing step catalysed by a bifunctional transmembrane kinase/endoribonuclease and tRNA ligase. This review describes the characterization of the UPR signalling pathway, focusing on the novel regulatory mechanisms that it has revealed.