The unfolded protein response: No longer just a special teams player

The endoplasmic reticulum stress pathway known as the unfolded protein resp onse is currently the best understood model of interorganellar signal trans duction. Bridging a physical separation, the pathway provides a direct line of communication between the endoplasmic reticulum lumen and the nucleus. With the unfolded protein response, the cell has the means to monitor and r espond to the changing needs of the endoplasmic reticulum. Beginning with t he discovery of its remarkable signaling mechanism in yeast, the unfolded p rotein response has not ceased to reveal more of its many secrets. By apply ing powerful biochemical, genetic, genomic, and cytological approaches, the recent efforts of many groups have buried the long-held notion that the un folded protein response is simply a regulatory platform for endoplasmic ret iculum chaperones. We now know that the unfolded protein response regulates many genes that affect diverse aspects of cellular physiology. In addition , studies in mammals have revealed novel unfolded protein response signalin g factors that may contribute to the specialized needs of multicellular org anisms. This article focuses on these and other recent developments in the field.