ribosome collisions Directly Trigger Cellular Stress Response, New Research Reveals
MUNICH, GERMANY – Scientists at the gene Center of Ludwig-Maximilians-Universität München (LMU) have discovered that colliding ribosomes are not merely a result of cellular stress, but the primary signal initiating the stress response.The breakthrough, published today in Nature, details how the protein ZAK recognizes these collisions and activates a signaling cascade crucial for cellular health and immune function.
For years,it’s been known that ZAK plays a key role in mediating the stress response,but how it detected the need for activation remained a mystery. Researchers, led by Prof. Dr. Roland Beckmann,used biochemical analyses and cryo-electron microscopy to demonstrate that ribosome collisions directly recruit and activate ZAK.The process involves ZAK interacting with specific ribosome proteins, causing it to dimerize – joining with another ZAK protein – and initiating the signaling pathway.
“A deeper understanding of these mechanisms is vital for several reasons,” explains Beckmann. “ZAK acts very early in the cellular stress response, so clarifying its recognition mechanisms provides important insights into how cells perceive disturbances with high temporal precision and how ribosomal quality control, the downstream signaling pathways and the immune response interact.”
The findings are significant because dysregulation of ZAK activity is linked to inflammatory diseases and chronic ribosome stress. This research establishes the translation machinery itself as a “monitoring platform” initiating global stress signals, offering a central principle in eukaryotic stress biology.
The study, titled “ZAK Activation at the Collided Ribosome,” was authored by V.L. Huso et al.and is available in Nature: https://www.nature.com/articles/s41586-025-09772-8.
Scientific Contact:
Prof. Dr. Roland Beckmann
Gene Center and Department of Biochemistry
Tel.: +49 89 2180-76900
beckmann@genzentrum.lmu.de
https://www.genzentrum.uni-muenchen.de/research-groups/beckmann/index.html
