Welcome to the map of short-lived proteins!

Rapid protein degradation enables cells to quickly modulate protein abundance in response to stimuli. Dysregulation of short-lived proteins often plays essential roles in disease pathogenesis. A focused map of short-lived proteins, however, has remained under-studied. Cycloheximide, a global translation inhibitor, has been widely used in targeted studies to measure degradation kinetics for short-lived proteins under translational arrest. Here, we combined cycloheximide chase assays with advanced high-throughput quantitative proteomics to map short-lived proteins under translation inhibition in four genetically distinct human cell lines. Among 11,747 quantified proteins, we identified 1,017 short-lived proteins with half-lives less than 8 hours under translational arrest. We further quantified 103 proteins with widely different stabilities among cell lines. This study provides a large-scale resource of human short-lived proteins under translational arrest in cultured cells, leading to untapped avenues of protein regulation for therapeutic interventions.

Citations

The short-lived protein web resource was built by Jiaming Li.

For more information see the publication: Li et al. Molecular Cell (2021)

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