26S proteasome non-ATPase regulatory subunit 6 (PSMD6)

26S proteasome non-ATPase regulatory subunit 6 (PSMD6) is a protein encoded by the PSMD6 gene in humans. It is part of the "lid" subcomplex of the 19S regulatory particle in the 26S proteasome, a multiprotein complex responsible for ATP-dependent degradation of ubiquitinated proteins in the cytosol and nucleus[2][4]. The lid subcomplex, where PSMD6 (also known as Rpn7 or S10) resides, scaffolds other proteasomal subunits and participates in substrate recognition, gating, and delivery for proteolysis. The proteasome, through coordinated conformational changes, controls protein turnover, modulates cell cycle and transcription, participates in DNA damage response, and serves critical roles in stress and immune responses[1][2][3]. Aberrant proteasomal function, including PSMD6 or other regulatory subunits, has been implicated in various diseases such as cancer, neurodegenerative and autoimmune disorders, and cardiovascular diseases. While current proteasome-targeting drugs such as bortezomib do not act on individual subunits selectively, they inhibit overall proteasome activity, leading to clinical benefit in malignancies at the cost of safety challenges due to their widespread cellular role[3]. PSMD6 and its associated subunits also have diagnostic biomarker potential, for example as circulating proteasomes in autoimmune conditions[3].

Other names

PSMD6KIAA0107PFAAP4S10p44S10Rpn7SGA-113Mphosphonoformate immuno-associated protein 4proteasome regulatory particle subunit p44S10p42A26S proteasome regulatory subunit RPN726S proteasome regulatory subunit S10breast cancer-associated protein SGA-113M

Inhibition of proteasome-dependent protein degradation; leads to accumulation of ubiquitinated proteins and induction of apoptosis, especially in rapidly dividing cells (e.g., cancer)[3].