The BRD7-P53-SLC25A28 axis regulates ferroptosis in hepatic stellate cells

Zhang, Zili; Guo, Mei; Shen, Min; Kong, Desong; Zhang, Feng; Shao, Jiangjuan; Tan, Shanzhong; Wang, Shijun; Chen, Anping; Cao, Peng; Zheng, Shizhong

doi:10.1016/j.redox.2020.101619

Cited by 130 publications

(95 citation statements)

References 52 publications

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“…The activity of SLC25A28 in ferroptosis is regulated by the bromodomain-containing protein 7 (BRD7) tumor protein p53 (TP53) pathway. In hepatic stellate cells, ferroptosis inducers increase the expression of BRD7 by inhibiting its proteasome degradation ( Zhang et al, 2020 ). Upregulated BRD7 further promotes mitochondrial translocation of TP53 by directly binding to its N-terminal transactivation domain.…”

Section: Regulators Of Iron Metabolism In Ferroptosismentioning

confidence: 99%

Iron Metabolism in Ferroptosis

Chen

Kang

et al. 2020

Front. Cell Dev. Biol.

541

382

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Ferroptosis is a form of regulated cell death that is characterized by iron-dependent oxidative damage and subsequent plasma membrane ruptures and the release of damage-associated molecular patterns. Due to the role of iron in mediating the production of reactive oxygen species and enzyme activity in lipid peroxidation, ferroptosis is strictly controlled by regulators involved in many aspects of iron metabolism, such as iron uptake, storage, utilization, and efflux. Translational and transcriptional regulation of iron homeostasis provide an integrated network to determine the sensitivity of ferroptosis. Impaired ferroptosis is implicated in various iron-related pathological conditions or diseases, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. Understanding the molecular mechanisms underlying the regulation of iron metabolism during ferroptosis may provide effective strategies for the treatment of ferroptosis-associated diseases. Indeed, iron chelators effectively prevent the occurrence of ferroptosis, which may provide new approaches for the treatment of iron-related disorders. In this review, we summarize recent advances in the theoretical modeling of iron-dependent ferroptosis, and highlight the therapeutic implications of iron chelators in diseases.

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Section: Regulators Of Iron Metabolism In Ferroptosismentioning

confidence: 99%

Iron Metabolism in Ferroptosis

Chen

Kang

et al. 2020

Front. Cell Dev. Biol.

541

382

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“…Hence one hypothesis is that this mechanism contributes to the greater tolerance of cancer cells towards elevated ROS and avoids oxidative stress-induced cell death [ 47 ]. In addition, several pathways, including a series of SUMO target proteins Keap1/Nrf2 [ 48 , 49 ], P53 [ 50 ], BECN1 [ 51 ] and NF2/YAP [ 52 ], are modified with susceptibility to ferroptosis. Among them, the Nrf2 protein functions as an antioxidant transcript factor that is closely related to ferroptosis inhibition [ 53 ], and it can be SUMOylated at the conserved site K110 [ 48 , 49 ].…”

Section: Sumoylation-mediated Cell Deathmentioning

confidence: 99%

SUMOylation modification-mediated cell death

et al. 2021

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SUMOylation dynamically conjugates SUMO molecules to the lysine residue of a substrate protein, which depends on the physiological state of the cell and the attached SUMO isoforms. A prominent role of SUMOylation in molecular pathways is to govern the cellular death process. Herein, we summarize the association between SUMOylation modification events and four types of cellular death processes: apoptosis, autophagy, senescence and pyroptosis. SUMOylation positively or negatively regulates a certain cellular death pattern depending on specific conditions including the attached SUMO isoforms, disease types, substrate proteins and cell context. Moreover, we also discuss the possible role of SUMOylation in ferroptosis and propose a potential role of the SUMOylated GPX4 in the regulation of ferroptosis. Mapping the exact SUMOylation network with cellular death contributes to develop novel SUMOylation-targeting disease therapeutic strategies.

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“…Given that BRD7 is required for XAF1 transcription [ 26 ], BRD7 likely serves a tumor-suppressive role in NSCLC. BRD7 also induces ferroptosis in hepatic stellate cells [ 93 ], which raises the possibility that BRD7 also plays a role as a tumor suppressor by regulating cell death through iron-dependent accumulation of lipid hydroperoxides [ 94 ]. Furthermore, BRD7 is downregulated in hepatocellular carcinoma [ 43 ], while higher BRD7 expression levels are associated with improved survival of patients with hepatocellular carcinoma, pointing to a tumor-suppressive role of BRD7 in hepatocellular carcinoma.…”

Section: Brd7 In Cancermentioning

confidence: 99%

Emerging Roles of BRD7 in Pathophysiology

Park

Lee

2020

IJMS

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Bromodomain is a conserved structural module found in many chromatin-associated proteins. Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family, and was discovered two decades ago as a protein that is downregulated in nasopharyngeal carcinoma. Since then, BRD7 has been implicated in a variety of cellular processes, including chromatin remodeling, transcriptional regulation, and cell cycle progression. Decreased BRD7 activity underlies the pathophysiological properties of various diseases in different organs. BRD7 plays an important role in the pathogenesis of many cancers and, more recently, its roles in the regulation of metabolism and obesity have also been highlighted. Here, we review the involvement of BRD7 in a variety of pathophysiological conditions, with a focus on glucose homeostasis, obesity, and cancer.

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The BRD7-P53-SLC25A28 axis regulates ferroptosis in hepatic stellate cells

Cited by 130 publications

References 52 publications

Iron Metabolism in Ferroptosis

Iron Metabolism in Ferroptosis

SUMOylation modification-mediated cell death

Emerging Roles of BRD7 in Pathophysiology

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