Hats off to 20S proteasome substrate discovery

Uncapped free 20S proteasomes are abundant and active in cells, and yet their degraded intracellular protein substrates have remained underexplored. In their recent study, Sharon and colleagues (Pepelnjak et al, 2024 ) developed an advanced proteomics method (PiP-MS) to comprehensively explore 20S proteasome substrates in the human proteome. The substrates of uncapped free 20S proteasomes have remained underexplored. In their recent study, Sharon, Picotti and colleagues (Pepelnjak et al, 2024 ) develop a proteomics-based method (PiP-MS) and comprehensively explore 20S proteasome substrates in the human proteome.