Targeting p53 pathways: mechanisms, structures and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 1, 2023

The TP53 tumor suppressor is the most frequently altered gene in human cancers, and has been a major focus of oncology research. p53 protein transcription factor that can activate expression multiple target genes plays critical roles regulating cell cycle, apoptosis, genomic stability, widely regarded as "guardian genome". Accumulating evidence shown also regulates metabolism, ferroptosis, microenvironment, autophagy so on, all which contribute to suppression. Mutations not only impair its function, but confer oncogenic properties mutants. Since mutated inactivated malignant tumors, it very attractive for developing new anti-cancer drugs. However, until recently, was considered an "undruggable" little progress made with p53-targeted therapies. Here, we provide systematic review diverse molecular mechanisms signaling pathway how mutations impact progression. We discuss key structural features inactivation by mutations. In addition, efforts have therapies, challenges encountered clinical development.

Language: Английский

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Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones

Cell, Journal Year: 2023, Volume and Issue: 186(13), P. 2748 - 2764.e22

Published: June 1, 2023

Language: Английский

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Cell death

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 235 - 256

Published: Jan. 1, 2024

Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens eliminating infected can be induced genetically programmed suicide mechanisms apoptosis, necroptosis, pyroptosis, it a consequence dysregulated metabolism, as in ferroptosis. Here, we review signaling underlying each cell-death pathway, discuss how impaired excessive activation distinct processes promote disease, highlight existing potential therapies for redressing imbalances cell cancer other diseases.

Language: Английский

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The cell biology of ferroptosis

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

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A guide to cell death pathways

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 379 - 395

Published: Dec. 18, 2023

Language: Английский

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Understanding mechanisms of antioxidant action in health and disease

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(1), P. 13 - 33

Published: Sept. 15, 2023

Language: Английский

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FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D571 - D582

Published: Oct. 28, 2022

Abstract Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation lipid peroxidation. It closely linked to the pathophysiological processes in many diseases. Since our publication first ferroptosis database 2020 (FerrDb V1), new findings have been published. To keep up with rapid progress research and provide timely high-quality data, here we present successor, FerrDb V2. contains 1001 regulators 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, which 264 drivers, 238 suppressors, 9 markers, 110 unclassified genes; 380 substance 201 inducers 179 inhibitors. Compared V1, articles increase >300%, 175%, 50.5%. Circular RNA pseudogene novel V2, percentage non-coding increases 7.3% 13.6%. External gene-related data were integrated, enabling thought-provoking gene-oriented analysis In conclusion, V2 will help acquire deeper insights into ferroptosis. freely accessible at http://www.zhounan.org/ferrdb/.

Language: Английский

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Regulation of ferroptosis by lipid metabolism

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(12), P. 1077 - 1087

Published: July 3, 2023

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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Identification of essential sites of lipid peroxidation in ferroptosis

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 19(6), P. 719 - 730

Published: Feb. 6, 2023

Language: Английский

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