26S proteasome complex (26S proteasome)

The 26S proteasome complex is a 2.5 MDa multi-subunit molecular machine essential for maintaining protein homeostasis in eukaryotic cells by degrading polyubiquitinated proteins (Source: PubMed, PMID: 21850271). It is composed of a 20S core particle, which contains the catalytic sites, and one or two 19S regulatory particles that facilitate substrate recognition, deubiquitination, and unfolding (Source: UniProt). This complex plays a critical role in regulating the cell cycle, DNA repair, and signal transduction pathways by controlling the degradation of regulatory proteins like cyclins and IκB (Source: StatPearls). In oncology, the proteasome is a validated therapeutic target because malignant cells, particularly plasma cells in multiple myeloma, are highly sensitive to the accumulation of misfolded proteins (Source: NIH, National Cancer Institute). Drugs such as bortezomib and carfilzomib inhibit the chymotrypsin-like activity of the proteasome, inducing the unfolded protein response and subsequent apoptosis (Source: PubChem). Despite its clinical success, targeting the proteasome can lead to significant side effects, including peripheral neuropathy and hematological toxicities, necessitating careful patient management (Source: PubMed, PMID: 28103469).

Other names

30S proteasome complex26S multicatalytic endopeptidase complexUbiquitin-proteasome system (UPS)26S proteasome

Inhibition of the chymotrypsin-like activity of the beta-5 subunit (PSMB5) within the 20S core particle of the proteasome complex.