The tumor suppressor protein p53 and the ferroptosis network

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 surv...

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Bibliographic Details
Published in:Free radical biology & medicine 2019-03, Vol.133, p.162-168
Main Authors: Kang, Rui, Kroemer, Guido, Tang, Daolin
Format: Article
Language:English
Subjects:
Acetyltransferases - genetics
Amino Acid Transport System y+ - genetics
Autophagy
Cell death
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Dipeptidyl Peptidase 4 - genetics
Ferroptosis
Ferroptosis - genetics
Gene Expression Regulation - genetics
Humans
Iron - metabolism
Life Sciences
Lipid Peroxidation - genetics
Oxidative Stress - genetics
p53
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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. [Display omitted] •Ferroptosis is a form of regulated cell death.•p53 plays a dual role in ferroptosis.•p53 enhances ferroptosis through targeting SLC7A11, SAT1 or GLS2.•p53 suppresses ferroptosis through targeting DPP4 or CDKN1A.•Activation of autophagy promotes ferroptosis.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2018.05.074