Proteomic Characterization Of Ubiquitin Receptor Adrm1/Rpn13

Background and Rationale 20S proteasome-based therapies are the mainstay of treatment of patients with multiple myeloma (MM); however, resistance to proteasome inhibitor (PI) therapies commonly develops underlying relapse of disease. We showed that inhibition of 19S-associated ubiquitin receptor (UbR) ADRM1/Rpn13, upstream of 20S proteasome, inhibits MM cell growth and overcomes PI-resistance in MM. hRpn13 recognizes polyubiquitinated proteins and facilitates their disassembly via 19S-associated deubiquitinating enzyme UCHL5, allowing for protein degradation via 20S proteasomal catalytic activities. To date, however, hRpn13-modulated protein substrates and downstream signaling remains unclear. Here, we utilized multiplexed proteomics with tandem mass spectrometry; GeneOntology (GO) enrichment; as well as pathway database KEGG and Reactome to identify hRpn13-associated signaling molecules and delineate functionally significant biological pathways.