Proteasome 20S subunit beta 5 (PSMB5) (PSMB5)

The Proteasome 20S subunit beta 5 (PSMB5) is a critical catalytic component of the 20S core particle within the 26S proteasome complex [5, 8]. It is primarily responsible for the "chymotrypsin-like" proteolytic activity, cleaving peptide bonds after large hydrophobic residues [5, 13]. As a central element of the ubiquitin-proteasome system (UPS), PSMB5 facilitates the degradation of misfolded, damaged, or short-lived regulatory proteins, thereby maintaining cellular protein homeostasis and regulating processes such as the cell cycle, signal transduction, and apoptosis [3, 6, 7].\n\nIn many malignancies, including multiple myeloma and various solid tumors, PSMB5 is frequently overexpressed, which supports the high metabolic and proliferative demands of cancer cells [1, 2, 12]. This subunit is the primary molecular target for several FDA-approved proteasome inhibitors, such as bortezomib and carfilzomib [3, 4, 13]. These drugs bind to the active site of PSMB5, leading to the accumulation of polyubiquitinated proteins, induction of endoplasmic reticulum stress, and ultimately, programmed cell death [2, 11]. However, clinical challenges include the development of resistance through PSMB5 point mutations or upregulation, as well as significant side effects like peripheral neuropathy [4, 10, 11].

Other names

MB1LMPXProteasome subunit XProteasome subunit beta type-5Beta-5Proteasome chain 6Macropain epsilon chainMulticatalytic endopeptidase complex epsilon chain

Inhibition of the chymotrypsin-like proteolytic activity of the 20S proteasome core particle, leading to the accumulation of polyubiquitinated proteins and induction of apoptosis [3, 13].