Abstract
and Rationale Proteasome inhibitors (PIs) represent major advance in the treatment of relapsed/refractory and newly diagnosed multiple myeloma (MM); however, PI-therapy is associated with adverse effects and the development of drug-resistance. Strategies to overcome PI-resistance include targeting ubiquitin proteasome system (UPS) upstream of 20S proteasome subunit. One such exemplary target is ubiquitin receptor PSMD4/Rpn10, which is localized on 19S regulatory lid of proteasome, and play a key role in recognizing ubiquitylated substrate proteins for degradation via downstream 20S proteasome.
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