Article abstract
Nature Structural & Molecular Biology 15, 1246 - 1254 (2008)
Published online: 16 November 2008 | doi:10.1038/nsmb.1516
Bach1 inhibits oxidative stress–induced cellular senescence by impeding p53 function on chromatin
Yoshihiro Dohi1,2,7, Tsuyoshi Ikura1, Yutaka Hoshikawa3, Yasutake Katoh1, Kazushige Ota1, Ayako Nakanome1, Akihiko Muto1, Shinji Omura2, Tsutomu Ohta4, Akihiro Ito5, Minoru Yoshida5,6, Tetsuo Noda3 & Kazuhiko Igarashi1
Abstract
Cellular senescence is one of the key strategies to suppress expansion of cells with mutations. Senescence is induced in response to genotoxic and oxidative stress. Here we show that the transcription factor Bach1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1), which inhibits oxidative stress-inducible genes, is a crucial negative regulator of oxidative stress–induced cellular senescence. Bach1-deficient murine embryonic fibroblasts showed a propensity to undergo more rapid and profound p53-dependent premature senescence than control wild-type cells in response to oxidative stress. Bach1 formed a complex that contained p53, histone deacetylase 1 and nuclear co-repressor N-coR. Bach1 was recruited to a subset of p53 target genes and contributed to impeding p53 action by promoting histone deacetylation. Because Bach1 is regulated by oxidative stress and heme, our data show that Bach1 connects oxygen metabolism and cellular senescence as a negative regulator of p53.
- Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan.
- Department of Cardiovascular Physiology and Medicine, Hiroshima University Graduate School of Biomedical Science, Kasumi 1-2-3, Hiroshima 734-8551, Japan.
- Japanese Foundation for Cancer Research, Cancer Institute, Ariake 3-10-6, Tokyo 135-8550, Japan.
- Center for Medical Genomics, National Cancer Center Research Institute, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan.
- Chemical Genetics Laboratory, RIKEN, Wako, Saitama 351-0198, Japan.
- Japan Science and Technology Corporation (JST), CREST Research Project, Kawasaki, Saitama 332-0012, Japan.
- Present address: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan.
Correspondence to: Kazuhiko Igarashi1 e-mail: igarak@m.tains.tohoku.ac.jp
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