Proteasome regulatory particle non-ATPase 13 (RPN13) (RPN13)

Proteasome regulatory particle non-ATPase 13 (RPN13), also known as ADRM1, is a crucial ubiquitin receptor located in the 19S regulatory particle of the 26S proteasome (UniProt, Q16186). It plays a vital role in the ubiquitin-proteasome system (UPS) by binding polyubiquitinated substrates through its N-terminal Pru domain, facilitating their delivery to the proteasome for degradation (PubMed, 24103879). Additionally, RPN13 serves as a docking site for the deubiquitinating enzyme UCHL5, which helps regulate the rate of protein degradation by removing ubiquitin chains (NCBI Gene, 11039). RPN13 is frequently overexpressed in various malignancies, including multiple myeloma and ovarian cancer, where it supports the survival of cancer cells under high proteotoxic stress (PubMed, 28655774). Because of its specific role in substrate recognition, RPN13 has become an attractive therapeutic target for small-molecule inhibitors like RA190, which covalently bind to the Pru domain and trigger apoptosis in cancer cells by blocking protein degradation (PubMed, 24103879). Targeting RPN13 offers a potential strategy to overcome resistance to existing proteasome inhibitors like bortezomib, which target the catalytic 20S core (PubMed, 28655774).

Other names

ADRM1Adhesion regulating molecule 1ARM-1GP11026S proteasome regulatory subunit RPN13hRpn13

Inhibition of the Pru domain to prevent ubiquitin binding and subsequent degradation of polyubiquitinated proteins, leading to proteotoxic stress and apoptosis.