RAW files, mzML files, search results (gpm.xml), TPP analysis files (pep.XML and prot.XML, as well as tab delimited output of pep.XML as .xls) and analyzed results Table 1 for the identification of BTRCP1/2 substrates using BioID. The identification of ubiquitin E3 ligase substrates has been extremely challenging, due in part to low-affinity, transient interactions, the rapid degradation of targets, and the inability to identify proteins from poorly soluble cellular compartments. SCF-TrCP1 and SCF-TrCP2 are well studied ubiquitin E3 ligases that target substrates for proteasomal degradation, and play important roles in Wnt, Hippo and NFB signalling. Combining 26S proteasome inhibitor (MG132) treatment with proximity-dependent biotin labeling (BioID) and semi-quantitative mass spectrometry, here we identify SCF-TrCP1/2 interacting partners. Based on their enrichment in the presence of MG132, our data identify over 50 new putative SCF-TrCP1/2 substrates. We validate 12 of these new substrates, and reveal previously unsuspected roles for -TrCP in the maintenance of nuclear membrane integrity, processing (P)-body turnover, and translational control. Together, our data suggest that -TrCP is an important hub in the cellular stress response. The approach presented here should be broadly applicable for the identification of substrates for many ubiquitin E3 ligases.