Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin.
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.
Dohi
Yoshihiro
Y
Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Sendai 980-8575, Japan.
Ikura
Tsuyoshi
T
Hoshikawa
Yutaka
Y
Katoh
Yasutake
Y
Ota
Kazushige
K
Nakanome
Ayako
A
Muto
Akihiko
A
Omura
Shinji
S
Ohta
Tsutomu
T
Ito
Akihiro
A
Yoshida
Minoru
M
Noda
Tetsuo
T
Igarashi
Kazuhiko
K
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D002452:Cell Count; D049109:Cell Proliferation; D016922:Cellular Senescence; D002843:Chromatin / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D018384:Oxidative Stress; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D002843:Chromatin; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases