TSPYL2 is a novel regulator of SIRT1 and p300 activity in response to DNA damage

Magni, Martina; Buscemi, Giacomo; Maita, Lucia; Lei, Peng; Chan, Sum‐Yin; Montecucco, Alessandra; Delia, Domenico; Zannini, Laura

doi:10.1038/s41418-018-0168-6

Cited by 41 publications

(39 citation statements)

References 43 publications

(73 reference statements)

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“…3), which is due to an increase in miR199-5p levels. Our data indicate that increased Sirt1 levels negatively regulate the activity of P300 40,41 . P300 is a transcriptional coactivator that functions as an integrator of numerous signaling pathways, and it regulates many DNA-binding proteins to facilitate transcriptional activation 42 .…”

Section: Discussionmentioning

confidence: 62%

The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI

Asensio-López

Sassi

Soler

et al. 2021

Sci Rep

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Left ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.

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Section: Discussionmentioning

confidence: 62%

The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI

Asensio-López

Sassi

Soler

et al. 2021

Sci Rep

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“…Dcun1d1 regulates matrix formation and cell growth (Fu et al 2016). Upf2, Smg1, and Tspyl2 participate in mRNA decay (Melero et al 2014;Magni et al 2019).…”

Section: Mir-361-3p Directly Targets Nfat5 In Cementoblastsmentioning

confidence: 99%

MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation

et al. 2019

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The development of periodontal tissue is a complex process, including cementoblast proliferation and differentiation. Emerging reports suggest that microRNAs (miRNAs) play crucial roles in gene regulatory networks governing numerous biological processes. However, how miRNAs modulate cementoblast proliferation and differentiation remains largely unknown. In a previous study, we performed miRNA microarray profiling to fully reveal the expression patterns of miRNAs involved in cementoblast differentiation. We focused on miR-361-3p, which decreased during cementoblast differentiation. Overexpression of miR-361-3p resulted in decreased cementoblast differentiation, whereas the functional inhibition of miR-361-3p yielded the opposite effect. The bioinformatics approach identified nuclear factor of activated T-cell 5 ( Nfat5) as a potential target of miR-361-3p, which was further verified by dual luciferase assay. Meanwhile, the expression pattern of Nfat5 was verified both in vitro and in vivo. Furthermore, knockdown of Nfat5 mimicked the inhibitory effect of overexpressing miR-361-3p in cementoblasts. Moreover, multiple signaling pathways, including the Erk1/2, JNK, p38, PI3K-Akt, and NF-κB pathways, were notably activated, and the Wnt/ß-catenin pathway was blocked by downregulation of Nfat5 or forced expression of miR-361-3p in cementoblast differentiation. Finally, the complementary approach demonstrated that miR-361-3p regulated cementoblast differentiation via or partially via Erk1/2 and PI3K-Akt. Overall, our study elucidated that the JNK, p38, NF-κB, and Wnt/ß-catenin pathways act as balancing players in the miR-361-3p/ Nfat5 signaling axis during cementoblast differentiation.

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“…SIRT1 is widely recognized as a crucial epigenetic regulator involved in many biological processes, including metabolism, genomic stability maintenance, reprograming, aging, and tumorigenesis, among others [39,40,41]. SIRT1 expression and its deacetylase activity are controlled in normal cells by other proteins, such as p53, testis-specific protein Y-encoded-like 2 (TSPYL2), CHK2, hipermethylated in cancer 1 (HIC1), and cell cycle apoptosis regulator 2 (CCAR2 or DBC1) [40,41,42,43,44].…”

Section: Introductionmentioning

confidence: 99%

The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer

Alves-Fernandes

Jasiulionis

2019

IJMS

251

147

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Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC), an NAD+-dependent enzyme deeply involved in gene regulation, genome stability maintenance, apoptosis, autophagy, senescence, proliferation, aging, and tumorigenesis. It also has a key role in the epigenetic regulation of tissue homeostasis and many diseases by deacetylating both histone and non-histone targets. Different studies have shown ambiguous implications of SIRT1 as both a tumor suppressor and tumor promoter. However, this contradictory role seems to be determined by the cell type and SIRT1 localization. SIRT1 upregulation has already been demonstrated in some cancer cells, such as acute myeloid leukemia (AML) and primary colon, prostate, melanoma, and non-melanoma skin cancers, while SIRT1 downregulation was described in breast cancer and hepatic cell carcinomas. Even though new functions of SIRT1 have been characterized, the underlying mechanisms that define its precise role on DNA damage and repair and their contribution to cancer development remains underexplored. Here, we discuss the recent findings on the interplay among SIRT1, oxidative stress, and DNA repair machinery and its impact on normal and cancer cells.

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TSPYL2 is a novel regulator of SIRT1 and p300 activity in response to DNA damage

Cited by 41 publications

References 43 publications

The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI

The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI

MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation

The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer

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