The versatility of the proteasome in gene expression and silencing: Unraveling proteolytic and non-proteolytic functions

The 26S proteasome consists of a 20S core particle and a 19S regulatory particle and critically regulates gene expression and silencing through both proteolytic and non-proteolytic functions. The 20S core particle mediates proteolysis, while the 19S regulatory particle performs non-proteolytic functions. The proteasome plays a role in regulating gene expression in euchromatin by modifying histones, activating transcription, initiating and terminating transcription, mRNA export, and maintaining transcriptome integrity. In gene silencing, the proteasome modulates the heterochromatin formation, spreading, and subtelomere silencing by degrading specific proteins and interacting with anti-silencing factors such as Epe1, Mst2, and Leo1. This review discusses the proteolytic and non-proteolytic functions of the proteasome in regulating gene expression and gene silencing-related heterochromatin formation. This article is part of a special issue on the regulation of gene expression and genome integrity by the ubiquitin-proteasome system.