Cellular senescence prevents the aberrant proliferation of damaged cells. The 
transcription factor Bach1 binds to p53 to repress cellular senescence, but it 
is still unclear how the Bach1-p53 interaction is regulated. We found that the 
Bach1-p53 interaction was inhibited by oncogenic Ras, bleomycin, and hydrogen 
peroxide. Proteomics analysis of Bach1 complex revealed its interaction with 
p19(ARF), a tumor suppressor that competitively inhibited the Bach1-p53 
interaction when overexpressed within cells. Reduction of MDM2 expression in 
wild-type murine embryonic fibroblasts (MEFs) did not result in slower 
proliferation, showing that Bach1 plays a role in keeping the proliferation of 
MEFs independent of MDM2. Consistent with this interpretation, expression of p21 
was highly induced in MEFs when both Bach1 and MDM2 were abrogated. The level of 
Bach1 protein was reduced on knockdown of p53. These results suggest that p53 
activation involves its dissociation from Bach1, achieved in part by the 
competitive binding of p19(ARF) to Bach1. The p19(ARF)-Bach1 interaction 
constitutes a regulatory pathway of p53 in parallel with the p19(ARF)-MDM2 
pathway.