Senescent cells form nuclear foci that contain the 26S proteasome

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. [Display omitted] •Senescent cells form senescence-associated nuclear proteasome foci (SANPs)•SANPs exhibit liquid-like properties•Active 26S proteasome, ubiquitin chains, and RAD23B are required for SANP formation•RAD23B knockdown suppresses SANPs and increases mitochondrial activity Iriki et al. find that senescent cells form senescence-associated nuclear proteasome foci (SANPs) that exhibit liquid-like properties and contain the active 26S proteasome, RAD23B, and ubiquitinated proteins. Knockdown of RAD23B suppresses SANP formation and increases mitochondrial activity and ROS production in senescent cells.