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Regulation of AIF by p53

We identified the gene encoding AIF as a potential target for positive regulation by p53. The AIF protein is an important player in apoptosis, through its ability to translocate from its normal mitochondrial location into the cell nucleus, where it can induce DNA fragmentation and cell death. We found that the AIF is positively regulated by p53 under basal conditions, namely even in the absence of overt DNA damage or other types of stress.

This is unusual in the sense that most known p53 target genes are selectively induced by p53 in response to genotoxic stresss, whereas such stress has very little effect on AIF levels. We show that AIF transcriptional induction is part of the arsenal that allows p53 to promote apoptosis in response to chemotherapy. Understanding the precise relationship between p53 and AIF may serve to optimize the selective impact of chemotherapy.

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