Pausing to decide.

Abstract

Sudden environmental changes and physiological stresses such as osmotic shock, nutrient availability, and heat shock demand that cells have the abilities to modulate their behavior to adapt and survive. Eukaryotic cells face the additional challenges of coordinating these changes between different cellular compartments, and this coordination necessitates interorganelle signaling pathways. For example, in times of stresses in the endoplasmic reticulum (ER), adaptive changes must be coordinated among protein folding capacity in the ER, transcription in the nucleus, and cytosolic synthesis of the proteins for the ER chaperons and protein processing enzymes. The pathway responsible for communicating these changes is called the unfolded protein response (UPR), ultimately leads to a significant remodeling of the entire secretory pathway in yeast. The UPR has proven remarkable both for the uniqueness of its signaling components and for the unprecedented mechanisms by which it is regulated (reviewed in refs. 1–3). In this issue of PNAS, the results of Brewer and Diehl (4) further our knowledge of mammalian UPR and its role in a complex cascade of cellular responses induced by unfolded proteins (5). More specifically, Brewer and Diehl (4) link a UPR-induced G1 cell cycle arrest with a protein phosphorylation pathway known to globally repress protein translation.