P53 and Sirt1: Routes of metabolism and genome stability

Gonfloni, Stefania; Iannizzotto, Valentina; Maiani, Emiliano; Bellusci, Giovanna; Ciccone, Sarah; Diederich, Marc

doi:10.1016/j.bcp.2014.08.034

Cited by 72 publications

(54 citation statements)

References 114 publications

(132 reference statements)

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“…Moreover, the p53 family could also be linked to ageing at the organism level [146,160]. Other emerging roles of p53 in glucose and lipid metabolism, ROS signalling and oxidative stress [64] suggest a significant functional overlap with SIRT pathways. p53 undergoes extensive post-translational modifications of several types; this makes it sensitive inter alia to inhibition and destabilisation via sirtuin-catalysed deacetylation (Figs.…”

Section: Transcriptional and Post-transcriptional Regulators As Sirtumentioning

confidence: 99%

“…The targets of SIRT1, which is by far the best characterized sirtuin, include histones, a broad range of stress signalling proteins, and transcription factors (TFs) ( Table I). SIRT1 is mainly involved in the regulation of the stress response and macromolecular repair (through its influence on p53 [64], heat shock factor HSF1 [114], forkhead box subgroup O -FOXO proteins [25], peroxisome proliferator-activated receptor -PPAR family [159], Ku70 [85]), anti-inflammatory response (via NF-κB [136,230]), exerts a pro-survival influence (through IIS -insulin/ IGF-I signalling [210]), and modulates the generation of mitochondria [66]. Long-term experimental SIRT1 activation in vivo is able to retard the onset of agerelated metabolic stress and mortality [136].…”

Section: Introductionmentioning

confidence: 99%

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Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Jęśko¹,

Strosznajder²

2016

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A b s t r a c tSirtuins vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-κB, and DNA-PK (DNA-dependent protein kinase). Sirtuins also interact extensively with the family of poly(ADPribose) polymerases (PARPs), a crucial and widespread class of NAD

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Section: Transcriptional and Post-transcriptional Regulators As Sirtumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Jęśko¹,

Strosznajder²

2016

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“…P53 translocation from the cytosol to the mitochondria occurs in response to high levels of ROS. P53 accumulation into mitochondria may lead to transcription-independent apoptosis (reviewed in (Gonfloni et al, 2014)). Recent findings from TAp63 or TAp73 null mice highlight the pivotal role of both factors in metabolism.…”

Section: P63: a Link Between Genomic Stability And Metabolism?mentioning

confidence: 99%

P63 in health and cancer

Gonfloni

Caputo²,

Iannizzotto³

2015

Int. J. Dev. Biol.

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TP63 is the most ancient member of the p53 gene family. The p53 family comprises three transcription factors (p53/p63/p73). They share a high degree of homology and similar domain structure. Yet, they can exist as truncated isoforms. Alternative promoters and splicing sites lead to the generation of several molecules. P53/p63/p73 are important to maintain cell homeostasis. P63 and p73 regulate many p53 target genes. This is due to their common structural features. Both proteins may compensate the loss of p53. This is a common event occurring in more than 50% of malignancies. Yet, p63 (or p73) has its own role. Studies from p63-null mice have shown the key role of p63 in embryo development. Several reports have supported the p63 role in epidermal development and in skin homeostasis. P63 involvement in heart development is currently being researched. Recent studies have found p63 to be "the guardian of human reproduction". In addition, p63 has an important, even controversial, role in cancer. Here, we provide a general overview of p63 regulation and activity. We discuss emerging concepts about its role in germ line protection, metabolism and cancer.

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“…Silent mating-type information regulator 2 homolog 1(SIRT 1) is an NAD + -dependent histone deacetylase, which plays a critical role in many cellular pathways, such as aging, metabolism, stress, and apoptosis [24,25]. Furthermore, elevated intracellular NAD+ level activate the SIRT1-dependent metabolic pathways [26].…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

Feng

Liú

et al. 2018

Cell Physiol Biochem

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Background/Aims: Myocardial ischemia/reperfusion (MI/R) injury is a leading factor responsible for damage in myocardial infarction, resulting in additional injury to cardiac tissues involved in oxidative stress, inflammation, and apoptosis. Thymoquinone (TQ), the main constituent of Nigella sativa L. seeds, has been reported to possess various biological activities. However, few reports regarding myocardial protection are available at present. Therefore, this study was conducted aiming to investigate the protective effect of TQ against MI/R injury and to clarify its potential mechanism. Methods: MI/R injury models of isolated rat hearts and neonatal rat cardiomyocytes were established. The Langendorff isolated perfused heart system, triphenyltetrazolium chloride staining, gene transfection, TransLaser scanning confocal microscopy, and western blotting were employed to evaluate the cardioprotection effect of TQ against MI/R injury. Results: Compared with the MI/R group, TQ treatment could remarkably improve left ventricular function, decrease myocardial infarct size and production of lactate dehydrogenase (LDH), and attenuate mitochondrial oxidative damage by elevating superoxide dismutase (SOD) activity and reducing production of hydrogen peroxide (H₂O₂) and malonaldehyde (MDA). Moreover, the cardioprotective effect of TQ was accompanied by up-regulated expression of SIRT1 and inhibition of p53 acetylation. Additionally, TQ treatment could also enhance mitochondrial function and reduce the number of apoptotic cardiomyocytes. Nonetheless, the cardioprotective effect of TQ could be mitigated by SIRT1 inhibitor sirtinol and SIRT1 siRNA, respectively, which was achieved through inhibition of the SIRT1 signaling pathway. Conclusions: The findings in this study demonstrate that TQ is efficient in attenuating MI/R injury through activation of the SIRT1 signaling pathway, which can thus reduce mitochondrial oxidative stress damage and cardiomyocyte apoptosis.

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P53 and Sirt1: Routes of metabolism and genome stability

Cited by 72 publications

References 114 publications

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

P63 in health and cancer

Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

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