The unfolded protein response (UPR), which occurs subsequent to the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), transmits a stress signal that arrests the cell cycle in G1. The ER-localized transmembrane protein kinase PERK, implicated in UPR, can phosphorylate the ribosomal protein eukaryotic initiation factor 2α (eIF2α), which leads to decreased protein translation. However, the products whose translation is inhibited in UPR have not been identified, for the most part. Brewer and Diehl found that the activation of PERK correlated with decreased levels of cyclin D1, a protein required for CDK4 catalytic activity and for progression through the G1 phase. Overexpression of PERK resulted in greater phosphorylation of eIF2α and decreased translation of cyclin D1 mRNA. However, overexpression of catalytically inactive PERK, in the presence of ER stress, inhibited the reduction of cyclin D1, and relieved cell-cycle arrest. These results suggest that PERK functions to connect ER stress with growth arrest regulation, by lowering the levels of cyclin D1 and blocking cell-cycle progression to S phase.