Proteasomal ubiquitin receptor ADRM1 (ADRM1) (ADRM1)

The Proteasomal ubiquitin receptor ADRM1 (also known as Rpn13) is a critical component of the 19S regulatory particle of the 26S proteasome. Its primary biological function is to recognize and bind polyubiquitinated proteins, facilitating their entry into the proteasome for degradation (UniProt: Q16186). This process is essential for maintaining cellular proteostasis and regulating various signaling pathways, including the cell cycle and apoptosis. In many cancers, ADRM1 is overexpressed, which correlates with poor prognosis and promotes the survival of malignant cells by managing high levels of proteotoxic stress (PubMed: 28655774). Consequently, ADRM1 has emerged as a promising therapeutic target, particularly in hematological malignancies like multiple myeloma. Small molecule inhibitors, such as RA190, target the N-terminal Pru domain of ADRM1, effectively blocking the degradation of ubiquitinated substrates and inducing apoptosis in cancer cells (PubMed: 24402044).

Other names

Rpn13Adhesion regulating molecule 1GP110ARM-1Regulatory particle non-ATPase 13Proteasome 26S subunit non-ATPase 13

Inhibition of the ubiquitin-binding Pru domain of ADRM1, preventing the recognition and degradation of polyubiquitinated proteins, leading to proteotoxic stress and apoptosis.