論文

査読有り
2017年2月

The SETD8/PR-Set7 Methyltransferase Functions as a Barrier to Prevent Senescence-Associated Metabolic Remodeling

CELL REPORTS
  • Hiroshi Tanaka
  • ,
  • Shin-ichiro Takebayashi
  • ,
  • Akihisa Sakamoto
  • ,
  • Tomoka Igata
  • ,
  • Yuko Nakatsu
  • ,
  • Noriko Saitoh
  • ,
  • Shinjiro Hino
  • ,
  • Mitsuyoshi Nakao

18
9
開始ページ
2148
終了ページ
2161
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.celrep.2017.02.021
出版者・発行元
CELL PRESS

Cellular senescence is an irreversible growth arrest that contributes to development, tumor suppression, and age-related conditions. Senescent cells show active metabolism compared with proliferating cells, but the underlying mechanisms remain unclear. Here we show that the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), suppresses nucleolar and mitochondrial activities to prevent cellular senescence. SETD8 protein was selectively downregu-lated in both oncogene-induced and replicative senescence. Inhibition of SETD8 alone was sufficient to trigger senescence. Under these states, the expression of genes encoding ribosomal proteins (RPs) and ribosomal RNAs as well as the cyclin-dependent kinase (CDK) inhibitor p16(INK4A) was increased, with a corresponding reduction of H4K20me1 at each locus. As a result, the loss of SETD8 concurrently stimulated nucleolar function and retinoblastoma protein-mediated mitochondrial metabolism. In conclusion, our data demonstrate that SETD8 acts as a barrier to prevent cellular senescence through chromatin-mediated regulation of senescence-associated metabolic remodeling.

Web of Science ® 被引用回数 : 24

リンク情報
DOI
https://doi.org/10.1016/j.celrep.2017.02.021
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000397328400009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.celrep.2017.02.021
  • ISSN : 2211-1247
  • Web of Science ID : WOS:000397328400009

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