26S proteasome non-ATPase regulatory subunit 2 (PSMD2)

26S proteasome non-ATPase regulatory subunit 2 (PSMD2, also known as Rpn1) is an essential scaffold and substrate receptor within the base subcomplex of the 19S regulatory particle of the 26S proteasome. PSMD2 mediates recognition and docking of ubiquitinated proteins destined for ATP-dependent degradation, thus orchestrating the first step of protein substrate processing by the proteasome. It offers critical docking sites for shuttle proteins (e.g., Rad23, Dsk2) involved in ubiquitin-dependent and independent trafficking of proteins to the degradation complex[4][1]. PSMD2 is also implicated in pathways regulating cell cycle, apoptosis, and MHC I antigen presentation. Alterations in PSMD2 expression or function have been associated with tumor progression and poor prognosis in cancers such as lung cancer[4]. Recent research has led to the development of peptidic macrocycles capable of binding PSMD2, motivating the evaluation of direct proteasomal recruitment as a therapeutic modality for targeted protein degradation[2].

Other names

Rpn1S2TRAP2P9755.11 proteinTumor necrosis factor type 1 receptor-associated protein 226S proteasome subunit p97MGC1427426S proteasome regulatory subunit Rpn126S proteasome regulatory subunit S2

Targeted protein degradation via direct recruitment to the 26S proteasome through PSMD2 binding[2]. General mechanism: Blockade of proteasome function leading to impaired degradation of ubiquitinated proteins.