The Proteasome 26S Subunit, Non-ATPase 11 (PSMD11), also known as RPN6, is a crucial component of the 26S proteasome complex in humans. This subunit plays a significant role in the ATP-dependent degradation of ubiquitinated proteins, which is essential for maintaining cellular homeostasis by removing misfolded, damaged, or unneeded proteins .
The 26S proteasome is a large, multi-catalytic proteinase complex composed of two main subcomplexes: the 20S core particle and the 19S regulatory particle. The 20S core is made up of four rings of 28 non-identical subunits, while the 19S regulatory particle consists of a base and a lid. PSMD11 is a non-ATPase subunit located in the lid of the 19S regulatory particle .
PSMD11 is involved in the assembly and stability of the 26S proteasome. It is particularly important in embryonic stem cells, where its high expression promotes enhanced proteasome activity, which is crucial for the rapid turnover of proteins during cell differentiation and development .
The 26S proteasome, including PSMD11, is vital for numerous cellular processes, such as:
Mutations or dysregulation of PSMD11 and other proteasome subunits have been associated with various diseases, including cancer and neurodegenerative disorders. For instance, altered proteasome activity can lead to the accumulation of damaged proteins, contributing to the pathogenesis of diseases like Alzheimer’s and Parkinson’s .
Given its central role in protein homeostasis, the proteasome, including PSMD11, is a target for therapeutic interventions. Proteasome inhibitors, such as bortezomib, are already used in the treatment of multiple myeloma and other cancers. Understanding the specific functions and regulation of PSMD11 could lead to the development of more targeted therapies for a range of diseases .