26S proteasome non-ATPase regulatory subunit 3 (PSMD3)

26S proteasome non-ATPase regulatory subunit 3 (PSMD3) is a protein component of the 19S regulatory particle of the 26S proteasome, a multi-protein complex that mediates ATP-dependent degradation of ubiquitinated proteins in the cytosol and nucleus. PSMD3 plays an essential role in cellular protein homeostasis, cell cycle progression, apoptosis, and DNA damage repair, and is involved in the regulation of immune and inflammatory responses through its effects on MHC class I peptide processing and immune cell traits. Dysregulation of PSMD3 expression and activity is associated with several diseases, notably multiple cancers (such as breast cancer and chronic myeloid leukemia), where it impacts disease progression, drug resistance, and prognosis. While selective inhibitors for PSMD3 are not available, it is targeted indirectly by general proteasome inhibitors, which are used therapeutically in certain malignancies.

Other names

PSMD3S3P58Rpn326S proteasome regulatory subunit S3Proteasome subunit p58Tissue specific transplantation antigen 226S proteasome regulatory subunit RPN3

Inhibition of proteasomal protein degradation; Induction of apoptosis via accumulation of misfolded proteins and inhibition of survival signals; Sensitization to chemotherapeutic agents by impairment of degradation of key regulatory proteins.