Senescent cells form nuclear foci that contain the 26S proteasome

Cell Rep. 2023 Aug 29;42(8):112880. doi: 10.1016/j.celrep.2023.112880. Epub 2023 Aug 3.


The proteasome plays a central role in intracellular protein degradation. Age-dependent decline in proteasome activity is associated with cellular senescence and organismal aging; however, the mechanism by which the proteasome plays a role in senescent cells remains elusive. Here, we show that nuclear foci that contain the proteasome and exhibit liquid-like properties are formed in senescent cells. The formation of senescence-associated nuclear proteasome foci (SANPs) is dependent on ubiquitination and RAD23B, similar to previously known nuclear proteasome foci, but also requires proteasome activity. RAD23B knockdown suppresses SANP formation and increases mitochondrial activity, leading to reactive oxygen species production without affecting other senescence traits such as cell-cycle arrest and cell morphology. These findings suggest that SANPs are an important feature of senescent cells and uncover a mechanism by which the proteasome plays a role in senescent cells.

Keywords: CP: Cell biology; CP: Molecular biology; cell senescence; liquid-liquid phase separation; mitochondria; nuclear body; proteasome; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus* / metabolism
  • Cellular Senescence
  • Proteasome Endopeptidase Complex* / metabolism
  • Ubiquitination


  • ATP dependent 26S protease
  • Proteasome Endopeptidase Complex