Immunoproteasome remodeling in senescing human macrophages reveals the loss of PA28αβ capping as a hallmark of immunosenescence.

ABSTRACT: Aging negatively impacts proteasome activity and/or content, and this impairment contributes to disrupted protein homeostasis and cellular dysfunction. However, little is known about proteasome complex dynamics during aging, particularly in the context of immunosenescence. Indeed, only limited data are available on the immunoproteasome, a specialized variant expressed in immune cells. We establish an in vitro model of monocyte-derived human macrophages that develop a senescence-like phenotype upon long-term culture. Our data demonstrate that immunoproteasome complexes undergo deep structural and functional alterations, with the downregulation of immunosubunit expression at the mRNA and protein level, uncapping of the 20S catalytic particle by the PA28αβ regulator, and loss of activity. Imm

SUBMITTER: Monittola F 

PROVIDER: S-EPMC12474951 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature