Activation of Maf/AP-1 repressor Bach2 by oxidative stress promotes apoptosis and its interaction with promyelocytic leukemia nuclear bodies.
The oxidative stress response operates by inducing the expression of genes that counteract the stress. We show here that the oxidative stress-responsive transcription factor Bach2 is a generic inhibitor of gene expression directed by the 12-O-tetradecanoylphorbol-13-acetate response element, the Maf recognition element, and the antioxidant-responsive element. The Bach2-enhanced green fluorescent protein bicistronic retrovirus was used to monitor the fate of Bach2-expressing cells at the single cell level. Bach2 exerted an inhibitory effect on NIH3T3 cell proliferation and caused massive apoptosis upon mild oxidative stress in both NIH3T3 and Raji B-lymphoid cells. Interestingly, Bach1, a highly homologous protein, could not induce cell death, demonstrating the specificity for the apoptosis induction. Although both oxidative stress and leptomycin B, an inhibitor of nuclear export, induce nuclear accumulation of Bach2, the leptomycin B-induced nuclear accumulation of Bach2 was not sufficient to elicit apoptosis. Upon oxidative stress, Bach2 formed nuclear foci that associated with promyelocytic leukemia nuclear bodies. Our results suggest that Bach2 constitutes a cell lineage-specific system that couples oxidative stress and cell death and that inhibition of 12-O-tetradecanoylphorbol-13-acetate response element, the Maf recognition element, and the antioxidant-responsive element upon oxidative stress may be critical determinants for apoptosis.
Muto
Akihiko
A
Department of Biochemistry, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan.
Tashiro
Satoshi
S
Tsuchiya
Haruka
H
Kume
Akihiro
A
Kanno
Masamoto
M
Ito
Etsuro
E
Yamamoto
Masayuki
M
Igarashi
Kazuhiko
K
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
C102109:Bach2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D012097:Repressor Proteins; D014157:Transcription Factors