Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Insults to ER homeostasis activate the unfolded protein response (UPR), which elevates protein folding and degradation capacity and attenuates protein synthesis. While a role for ubiquitin in regulating the degradation of misfolded ER-resident proteins is well described, ubiquitin-dependent regulation of translational reprogramming during the UPR remains uncharacterized. Using global quantitative ubiquitin proteomics, we identify evolutionarily conserved, site-specific regulatory ubiquitylation of 40S ribosomal proteins. We demonstrate that these events occur on assembled cytoplasmic ribosomes and are stimulated by both UPR activation and translation inhibition. We further show that ER stress-stimulated regulatory 40S ribosomal ubiquitylation occurs on a timescale similar to eIF2α phosphorylation, is dependent upon PERK signaling, and is required for optimal cell survival during chronic UPR activation. In total, these results reveal regulatory 40S ribosomal ubiquitylation as an important facet of eukaryotic translational control.

Original publication




Journal article


Molecular cell

Publication Date





35 - 49


Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.


Cell Line, Endoplasmic Reticulum, Animals, Humans, Drosophila, Saccharomyces cerevisiae, eIF-2 Kinase, Eukaryotic Initiation Factor-2, Cell Survival, Protein Biosynthesis, Gene Expression Regulation, Amino Acid Sequence, Phosphorylation, Molecular Sequence Data, Ribosome Subunits, Small, Eukaryotic, Ubiquitination, Unfolded Protein Response, Endoplasmic Reticulum Stress