Cell cycle–dependent localization of the proteasome to chromatin

• Published in: Scientific reports 2020-04, Vol.10 (1), p.5801-5801, Article 5801
• Main Authors: Kito, Yuki, Matsumoto, Masaki, Hatano, Atsushi, Takami, Tomoyo, Oshikawa, Kiyotaka, Matsumoto, Akinobu, Nakayama, Keiichi I.
• Format: Article
• Language: English
• Subjects: 631/45/474/2085; 631/45/475; Animals; Cell Cycle; Chromatin; Chromatin - metabolism; Diploids; Down-Regulation; Fibroblasts; Gene regulation; Humanities and Social Sciences; Humans; Localization; Mice; multidisciplinary; NIH 3T3 Cells; Proteasome 26S; Proteasome Endopeptidase Complex - metabolism; Protein Transport; Proteome - genetics; Proteome - metabolism; Proteomics; Science; Science (multidisciplinary); Transcription factors; Transformed cells; Translocation; Tumorigenesis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62697-2

An integrative understanding of nuclear events including transcription in normal and cancer cells requires comprehensive and quantitative measurement of protein dynamics that underlie such events. However, the low abundance of most nuclear proteins hampers their detailed functional characterization. We have now comprehensively quantified the abundance of nuclear proteins with the use of proteomics approaches in both normal and transformed human diploid fibroblasts. We found that subunits of the 26S proteasome complex were markedly down-regulated in the nuclear fraction of the transformed cells compared with that of the wild-type cells. The intranuclear proteasome abundance appeared to be inversely related to the rate of cell cycle progression, with restraint of the cell cycle being associated with an increase in the amount of proteasome subunits in the nucleus, suggesting that the nuclear proteasome content is dependent on the cell cycle. Furthermore, chromatin enrichment for proteomics (ChEP) analysis revealed enrichment of the proteasome in the chromatin fraction of quiescent cells and its apparent dissociation from chromatin in transformed cells. Our results thus suggest that translocation of the nuclear proteasome to chromatin may play an important role in control of the cell cycle and oncogenesis through regulation of chromatin-associated transcription factors.