C-terminal amides mark proteins for degradation via SCF-FBXO31.

ABSTRACT: During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts¹. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites^2,3. Such modifications have been proposed to trigger the selective removal of chemically marked proteins^3-6; however, identifying modifications that are sufficient to induce protein degradation has remained challenging. Here, using a semi-synthetic chemical biology approach coupled to cellular assays, we found that C-terminal amide-bearing proteins (CTAPs) are rapidly cleared from human cells. A CRISPR screen identified FBXO31 as a reader of

SUBMITTER: Muhar MF 

PROVIDER: S-EPMC11821526 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature