p53: A double-edged sword in tumor ferroptosis

Ji, Hong; Wang, Wenzhe; Li, Xia; Han, Xiaoying; Zhang, Xinyu; Wang, Juan; Liu, Changxiao; Huang, Lu-Qi; Gao, Wenyuan

doi:10.1016/j.phrs.2021.106013

Cited by 42 publications

(42 citation statements)

References 67 publications

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“…Its possible role in ferroptosis is associated with its ability to maintain a lower level of cellular GSH. TIGAR promotes NADPH production through the pentose phosphate pathway, which has an important role in regulating subsequent NADPH-related ferroptosis ( Ji et al, 2021 ).…”

Section: Molecular Mechanisms Of P53 In Ferroptosis-based Cancer Therapymentioning

confidence: 99%

“…p53 can also promote ferroptosis by influencing the function of ferredoxin reductase (FDXR) in iron metabolism ( Ji et al, 2021 ). FDXR is a mitochondrial flavoprotein that transfers electrons to ferredoxin 1 (FDX1) and FDX2 ( Brandt and Vickery, 1992 ); FDX1 is closely associated with steroidogenesis in mitochondria, while FDX2 is closely associated with cell survival.…”

Section: Molecular Mechanisms Of P53 In Ferroptosis-based Cancer Therapymentioning

confidence: 99%

“…In a recent study, p53-mediated CDKN1A expression delayed the onset of ferroptosis in response to subsequent cysteine deprivation in cancer cells ( Tarangelo et al, 2018 ). This may be associated with reduced ROS production and attenuated GSH consumption ( Ji et al, 2021 ). Importantly, that study was conducted in cells that had been pretreated with the p53 stabilizer nutlin-3; it remains unknown whether similar results can be achieved using other cells.…”

Section: Molecular Mechanisms Of P53 In Ferroptosis-based Cancer Therapymentioning

confidence: 99%

“…In addition to its effects on SLC7A11 suppression, p53 acetylation can regulate ferroptosis by regulating its downstream genes. Acetylation of p53 at K320 activates CDKN1A/p21, thereby delaying ferroptosis ( Abbas and Dutta, 2009 ; Ji et al, 2021 ); however, the underlying mechanism is unknown. According to one hypothesis, p21 acts on GSH, thereby increasing the synthesis of GSH and GPX4, decreasing lipid peroxide accumulation, and reducing cell sensitivity to ferroptosis.…”

Section: Effects Of P53 Ptms On Ferroptosismentioning

confidence: 99%

“…p53-mediated regulation of ferroptosis is closely associated with the levels of GPX4 and toxic peroxides. Therefore, p53 will affect cell sensitivity to ferroptosis by acting on p21 to control intracellular GSH levels, or by inhibiting SLC7A11 transcription (thereby increasing intracellular cysteine) ( Ji et al, 2021 ). However, extensive studies regarding the mechanistic importance of p53 acetylation in tumor suppression are needed to determine the contributions of these acetyltransferases to the control of p53-mediated ferroptosis.…”

Section: Effects Of P53 Ptms On Ferroptosismentioning

confidence: 99%

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Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy

et al. 2022

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The tumor suppressor p53 is a well-known cellular guardian of genomic integrity that blocks cell cycle progression or induces apoptosis upon exposure to cellular stresses. However, it is unclear how the remaining activities of p53 are regulated after the abrogation of these routine activities. Ferroptosis is a form of iron- and lipid-peroxide-mediated cell death; it is particularly important in p53-mediated carcinogenesis and corresponding cancer prevention. Post-translational modifications have clear impacts on the tumor suppressor function of p53. Here, we review the roles of post-translational modifications in p53-mediated ferroptosis, which promotes the elimination of tumor cells. A thorough understanding of the p53 functional network will be extremely useful in future strategies to identify pharmacological targets for cancer therapy.

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Section: Molecular Mechanisms Of P53 In Ferroptosis-based Cancer Therapymentioning

confidence: 99%

Section: Molecular Mechanisms Of P53 In Ferroptosis-based Cancer Therapymentioning

confidence: 99%

Section: Molecular Mechanisms Of P53 In Ferroptosis-based Cancer Therapymentioning

confidence: 99%

Section: Effects Of P53 Ptms On Ferroptosismentioning

confidence: 99%

Section: Effects Of P53 Ptms On Ferroptosismentioning

confidence: 99%

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Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy

et al. 2022

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Ferroptosis: A New Strategy for the Treatment of Fibrotic Diseases

Pei,

Fan,

Tang

et al. 2024

Advanced Biology

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Ferroptosis is a new type of cell death characterized by iron dependence and the excessive accumulation of lipid reactive oxygen species (lipid ROS) that has gradually become better characterized. There is sufficient evidence indicating that ferroptosis is associated with a variety of human life activities and diseases, such as tumor suppression, ischemic organ injury, and degenerative disorders. Notably, ferroptosis is also involved in the initiation and development of fibrosis in various organs, including liver fibrosis, pulmonary fibrosis, renal fibrosis, and cardiac fibrosis, which is usually irreversible and refractory. Although a large number of patients with fibrosis urgently need to be treated, the current treatment options are still limited and unsatisfactory. Organ fibrosis involves a series of complex and orderly processes, such as parenchymal cell damage, recruitment of inflammatory cells and activation of fibroblasts, which ultimately leads to the accumulation of extracellular matrix (ECM) and the formation of fibrosis. An increasing number of studies have confirmed the close association between these pathological processes and ferroptosis. This review summarizes the role and function of ferroptosis in fibrosis and proposes several potential therapeutic strategies and pathways based on ferroptosis.

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New molecular insights into ferroptosis in lung adenocarcinoma progression and pharmacological compounds for targeted therapy

Tian

Wan

Tian

et al. 2023

The Journal of Gene Medicine

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BackgroundThe involvement of ferroptosis has been found in many pathological conditions of the lung. The genetic engineering of ferroptosis‐related genes may provide a potential target for the treatment of lung adenocarcinoma (LUAD).MethodsNine ferroptosis regulators and markers were collected from FerrDb and their somatic mutations and expressions were analyzed based on The Cancer Genome Atlas (TCGA)‐LUAD cohort data. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were performed to screen genes significantly associated with ferroptosis. The ferroptosis‐related gene signature was constructed using TCGA‐LUAD cohort data and was verified using the GSE cohort with pooled data for GSE30219, GSE31210, GSE37745 and GSE50081. Immune microenvironment component and mutation analysis were performed for genes in the ferroptosis‐related gene signature.ResultsAll nine ferroptosis regulators and markers were differentially expressed between normal LUAD tumor tissues and adjacent normal tissues and were related to copy number variation. The expression of 1329 genes were significantly associated with nine ferroptosis regulators and markers in the TCGA‐LUAD dataset, five (ALDOA, PLK1, CD47, CENPC and TMOD3) of which were integrated into a ferroptosis‐related gene signature to calculate the risk score of LUAD samples, showing a significant correlation with the abundance of immune cell infiltration and the immune score. Molecular docking showed the binding activity of natural active compound quercetin to target proteins ALDOA and CD47, as well as the binding activity of aristolochic acid to PLK1 protein and TMOD3 protein.ConclusionsIn the present study, a ferroptosis‐related gene signature with predictive value for LUAD prognosis was constructed, in which the gene was a potential therapeutic target for LUAD. Quercetin and aristolochic acid were potential candidates for inhibiting these targets by directly binding to them and showing high affinity and strong stability.

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p53: A double-edged sword in tumor ferroptosis

Cited by 42 publications

References 67 publications

Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy

Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy

Ferroptosis: A New Strategy for the Treatment of Fibrotic Diseases

New molecular insights into ferroptosis in lung adenocarcinoma progression and pharmacological compounds for targeted therapy

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