Proteolytic degradation is critical to the maintenance of appropriate levels of short-lived and regulatory proteins as important and diverse as those involved in cellular metabolism, heat shock and stress response, antigen presentation, modulation of cell surface receptors and ion channels, cell cycle regulation, transcription, and signaling factors. The ubiquitin-proteasome pathway deconstructs most proteins in the eukaryotic cell cytosol and nucleus. Others are degraded via the vacuolar pathway which includes endosomes, lysosomes, and the endoplasmic reticulum.
The 26S proteasome is an ATP-dependent, multisubunit (~31), barrel-shaped molecular machine with an apparent molecular weight of ~2.5 MDa. It consists of a 20S proteolytic core complex which is crowned at one or both ends by 19S regulatory subunit complexes. The 19S regulatory subunits recognize ubiquitinated proteins and play an essential role in unfolding and translocating targets into the lumen of the 20S subunit. An enzymatic cascade is responsible for the attachment of multiple ubiquitin molecules to lysine residues of proteins targeted for degradation. Several genetic diseases are associated with defects in the ubiquitin-proteasome pathway. Some examples of affected proteins include those linked to cystic fibrosis, Angelman's syndrome, and Liddle syndrome.
26S proteasome non-ATPase regulatory subunit 7; 26S proteasome regulatory subunit RPN8; 26S proteasome regulatory subunit S12; Moloney leukemia virus-34 proviral integration; MOV34; Mov34 homolog; Mov34 protein; Mov34 protein homolog; proteasome (prosome, macropain) 26S subunit, non-ATPase, 7; proteasome (prosome, macropain) 26S subunit, non-ATPase, 7 (Mov34 homolog); Proteasome subunit p40; Rpn8