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Review
. 2019 Mar:133:162-168.
doi: 10.1016/j.freeradbiomed.2018.05.074. Epub 2018 May 23.

The tumor suppressor protein p53 and the ferroptosis network

Rui Kang  1 , Guido Kroemer  2 , Daolin Tang  3
Affiliations
Review

The tumor suppressor protein p53 and the ferroptosis network

Rui Kang et al. Free Radic Biol Med. 2019 Mar.

Abstract

Ferroptosis is a form of lipid peroxidation-induced cell death that can be regulated in many ways, from altering the activity of antioxidant enzymes to the level of transcription factors. The p53 tumor suppressor is 'the guardian of the genome' that participates in the control of cell survival and division under various stresses. Beyond its effects on apoptosis, autophagy, and cell cycle, p53 also regulates ferroptosis either through a transcriptional or posttranslational mechanism. On one hand, p53 can enhance ferroptosis by inhibiting the expression of SLC7A11 (solute carrier family 7 member 11) or by enhancing that of SAT1 (spermidine/spermine N1-acetyltransferase 1) and GLS2 (glutaminase 2). On the other hand, p53 suppresses ferroptosis through the direct inhibition of DPP4 (dipeptidyl peptidase 4) activity or by the induction of CDKN1A/p21 (cyclin dependent kinase inhibitor 1 A) expression. Here, we review recent discoveries and emerging trends in the study of the ferroptosis network and highlight the context-dependent impact of p53 on ferroptosis and oxidative stress.

Keywords: Autophagy; Cell death; Ferroptosis; p53.

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Figures

Figure 1
Figure 1
The dual role of p53 in the control of ferroptosis. Ferroptosis is characterized by lipid peroxidation. p53 plays a context-dependent role in the regulation of lipid peroxidation in ferroptosis. On one hand, p53 can enhance ferroptosis through the inhibition of SLC7A11 expression or promotion of SAT1 and GLS2 expression. On the other hand, p53 could suppress ferroptosis through the inhibition of DPP4 activity or induction of CDKN1A/p21 expression.
See this image and copyright information in PMC

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