Using the mitochondrial DUB USP30 as a case study, we recovered known substrates (TOMM20, FKBP8) and identified LETM1 as a novel USP30-regulated substrate. This method offers a valuable framework for dissecting DUB- and also E3-substrate interactions in native cellular contexts. Read the full article here.
Integrative Proxy-Ubiquitomics Profiling for Deubiquitinase Substrate Discovery Applied to USP30
21 May 2025
Andreas Damianou and Hannah Jones from the Kessler lab, together with the DisPro team, tackle the long-standing challenge of identifying direct deubiquitinase (DUB) substrates by combining APEX2-based proximity labeling with K-ε-GG ubiquitin remnant enrichment. This proximal-ubiquitomics approach enables site-specific, spatially resolved detection of deubiquitination events.