A novel link between p53 and ROS

He, Zhaoyue; Simon, Hans‐Uwe

doi:10.4161/cc.23418

Cited by 28 publications

(22 citation statements)

References 5 publications

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“…The oxidative damage to proteins eventually leads to inhibition of enzymatic/binding activities, increased susceptibility to aggregation and proteolysis, altered uptake by cells, and altered immunogenicity [43]. Several transcription factors (TFs) have been shown to be activated by ROS and amongst redox-regulated TFs, important examples are Forkhead homebox type O (FOXO) [44,45], nuclear factor E2-related factor 2 (Nrf2) [46,47], tumour suppressor 53 (p53) [48], nuclear factor kappa B (NF-κB) [49,50,51], activator protein-1 (AP-1) [52,53] and hypoxia inducible factor 1-a (HIF-1a) [54]. FOXO TFs can be viewed as molecular sensors for oxidative stress since their activity is regulated by H 2 O 2 .…”

Section: Oxidative Stress: Nox-rosmentioning

confidence: 99%

The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

Tarafdar

Pula

2018

IJMS

276

216

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For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation—primarily superoxide anion (O2●−), although hydrogen peroxide (H2O2) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.

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Section: Oxidative Stress: Nox-rosmentioning

confidence: 99%

The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

Tarafdar

Pula

2018

IJMS

276

216

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“…In contrast, ROS can modify p53 conformation to adjust the transcription of p53 42. In the current study, ROS was validated to play an important role in sinuleptolide-induced cell death of oral cancer cells.…”

Section: Discussionmentioning

confidence: 58%

“…p53 is reported to highly regulate redox homeostasis and to modulate several ROS-regulating genes 42. In contrast, ROS can modify p53 conformation to adjust the transcription of p53 42.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species mediate soft corals-derived sinuleptolide-induced antiproliferation and DNA damage in oral cancer cells

Huang

Tang

Liaw

et al. 2017

OTT

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We previously reported that the soft coral-derived bioactive substance, sinuleptolide, can inhibit the proliferation of oral cancer cells in association with oxidative stress. The functional role of oxidative stress in the cell-killing effect of sinuleptolide on oral cancer cells was not investigated as yet. To address this question, we introduced the reactive oxygen species (ROS) scavenger (N-acetylcysteine [NAC]) in a pretreatment to evaluate the sinuleptolide-induced changes to cell viability, morphology, intracellular ROS, mitochondrial superoxide, apoptosis, and DNA damage of oral cancer cells (Ca9-22). After sinuleptolide treatment, antiproliferation, apoptosis-like morphology, ROS/mitochondrial superoxide generation, annexin V-based apoptosis, and γH2AX-based DNA damage were induced. All these changes were blocked by NAC pretreatment at 4 mM for 1 h. This showed that the cell-killing mechanism of oral cancer cells of sinuleptolide is ROS dependent.

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“…Therefore our current data, although still preliminary, might indicate TAp73/BNIP3 negative axis as a novel pathway for TAp73 tumor suppressor 100,101 BNIP3 upregulation as a consequence of TAp73 loss might therefore contribute to TAp73-dependent mitochondrial phenotype and be associated to the complex involvement of p73 [102][103][104] and the other family members in regulation of mitochondrial activity, [105][106][107][108] cell metabolism [109][110][111][112][113][114] and redox homeostasis. [115][116][117][118] However, currently it is still unclear whether the complex integration of all the p53 family members, in particular the truncated isoform of p73, DNp73, and the cancer-associated mutants of p53, impacts and affects the TAp73-dependent antagonism of BNIP3 expression and more generally of hypoxia response. Future studies are demanded to address these aspects.…”

Section: Discussionmentioning

confidence: 99%

TAp73 transcriptionally represses BNIP3 expression

et al. 2015

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TAp73 is a tumor suppressor transcriptional factor, belonging to p53 family. Alteration of TAp73 in tumors might lead to reduced DNA damage response, cell cycle arrest and apoptosis. Carcinogen-induced TAp73 ¡/¡ tumors display also increased angiogenesis, associated to hyperactivition of hypoxia inducible factor signaling. Here, we show that TAp73 suppresses BNIP3 expression, directly binding its gene promoter. BNIP3 is a hypoxia responsive protein, involved in a variety of cellular processes, such as autophagy, mitophagy, apoptosis and necrotic-like cell death. Therefore, through different cellular process altered expression of BNIP3 may differently contribute to cancer development and progression. We found a significant upregulation of BNIP3 in human lung cancer datasets, and we identified a direct association between BNIP3 expression and survival rate of lung cancer patients. Our data therefore provide a novel transcriptional target of TAp73, associated to its antagonistic role on HIF signaling in cancer, which might play a role in tumor suppression.

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A novel link between p53 and ROS

Cited by 28 publications

References 5 publications

The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

Reactive oxygen species mediate soft corals-derived sinuleptolide-induced antiproliferation and DNA damage in oral cancer cells

TAp73 transcriptionally represses BNIP3 expression

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