Proteasomeassociated

Proteasome-associated is a term used to describe proteins that physically interact with the proteasome, the large protease complex responsible for targeted protein degradation in the ubiquitin–proteasome system. The functional proteasome consists of a core particle (20S) and regulatory particles (19S) that recognize ubiquitinated substrates. Proteins described as proteasome-associated may be integral subunits, regulatory cofactors, chaperones, adaptors, or enzymes that modulate proteasome activity or substrate processing. The association can be constitutive or transient and may be regulated by cellular conditions, ubiquitination status, or post-translational modifications.

Proteasome-associated proteins influence degradation by several mechanisms. Some are deubiquitinases (for example, USP14/Ubp6 and UCHL5) that trim ubiquitin chains or regulate access to the core particle; others are proteasome activators such as PA28 (PA28αβ and PA28γ) or PA200 that alter gate opening and proteolysis. Substrate shuttles like Rad23, Dsk2, and DDI1 bind ubiquitinated proteins and deliver them to the proteasome. Additional factors, such as Ecm29, can affect proteasome assembly or stability. Proteasome-associated proteins are studied to understand how protein turnover is regulated in response to cellular stress and to illuminate disease processes linked to proteostasis, including neurodegenerative disorders and cancer.