Senescent cells form nuclear foci that contain the 26S proteasome
Tomohiro Iriki,
Hiroaki Iio,
Shu Yasuda,
Shun Masuta,
Masakazu Kato,
Hidetaka Kosako,
Shoshiro Hirayama,
Akinori Endo,
Fumiaki Ohtake,
Mako Kamiya,
Yasuteru Urano,
Yasushi Saeki,
Jun Hamazaki,
Shigeo Murata
Affiliations
Tomohiro Iriki
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan
Hiroaki Iio
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan
Shu Yasuda
Department of Hygienic Chemistry and Medical Research Laboratories, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo 1088641, Japan
Shun Masuta
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan
Masakazu Kato
Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Nakano-ku, Tokyo 1648530, Japan
Hidetaka Kosako
Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Tokushima University, Kuramoto-cho, Tokushima 7708503, Japan
Shoshiro Hirayama
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan
Akinori Endo
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 1568506, Japan
Fumiaki Ohtake
Institute for Advanced Life Sciences, Hoshi University, Shinagawa-ku, Tokyo 1428501, Japan
Mako Kamiya
Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama 2268501, Japan
Yasuteru Urano
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan; Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan
Yasushi Saeki
Division of Protein Metabolism, the Institute of Medical Science, the University of Tokyo, Minato-ku, Tokyo 1088639, Japan
Jun Hamazaki
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan
Shigeo Murata
Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Bunkyo-ku, Tokyo 1130033, Japan; Corresponding author
Summary: 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.
