This research explores how cells terminate the integrated stress response (ISR) to resume normal protein synthesis. The study identifies that the protein R15B plays a critical role by facilitating the dephosphorylation of P-eIF2 while it is still attached to the translation factor eIF2B. Previously, it was unclear how this process occurred because the inhibited complex appeared structurally inaccessible to traditional repair mechanisms. Using advanced cryo-electron microscopy, the researchers demonstrated that R15B effectively "unlocks" the inhibited eIF2B, allowing it to become active again. This discovery provides a vital link in understanding cellular recovery, as failing to end the stress response can lead to cell death. Ultimately, the findings highlight a sophisticated molecular rescue operation that maintains cellular homeostasis and fitness.

References:

• De Miguel C, Thorkelsson S R, Fatalska A, et al. Termination of the integrated stress response[J]. Science, 2025: eadw5137.