Proteasome 26S subunit non-ATPase 5 (PSMD5)

Proteasome 26S subunit non-ATPase 5 (PSMD5, also known as S5B) is a chaperone-like non-catalytic component of the 19S regulatory base of the 26S proteasome complex, which is central to ATP/ubiquitin-dependent protein degradation in eukaryotic cells[1][3][4]. PSMD5 functions as a negative regulator of 26S proteasome assembly by interacting with assembly intermediates, thereby preventing premature or excessive assembly of the full proteasome complex[1][4][5]. In response to cellular stress (such as inflammatory stimuli mediated by TNF-α and the NFκB pathway), PSMD5 expression is upregulated, leading to reduced proteasome assembly and accumulation of polyubiquitinated proteins[1]. Conversely, cancer cells often downregulate PSMD5 to facilitate increased proteasome assembly and meet their elevated protein degradation needs, highlighting its potential as a context-dependent therapeutic target[5]. Modulation of PSMD5 function and expression not only controls cellular proteostasis but also influences cell fate in disease states including cancer and age-related proteotoxic disorders[5][1][3].

Other names

26S proteasome non-ATPase regulatory subunit 5KIAA0072S5B26S protease subunit S5 basic26S proteasome subunit S5Bproteasome (prosome, macropain) 26S subunit non-ATPase 5

Modulators of PSMD5 would regulate 26S proteasome assembly and thereby modulate proteasome activity—either by inhibiting assembly (through increased PSMD5) or enhancing assembly (through PSMD5 downregulation/inhibition)