The p53-p21-DREAM-CDE/CHR pathway regulates G<sub>2</sub>/M cell cycle genes

Fischer, Martin; Quaas, Marianne; Steiner, Lydia; Engeland, Kurt

doi:10.1093/nar/gkv927

Cited by 264 publications

(263 citation statements)

References 61 publications

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“…And knockdown of STAT3 or P53 inhibited the SEA-induced senescence of HSCs [12]. Besides the P53-P21 and P16-Rb signaling pathways [30–32], there are other signaling pathways that promoting the development and progression of cellular senescence. The inactivation of retinal vascular tumor suppressor factor (VHL) can decrease the expression of SKP2 and increase the expression of P27, and then induce cellular senescence [33].…”

Section: Discussionmentioning

confidence: 99%

Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway

et al. 2016

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BackgroundLiver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antigens (SEA) of Schistosoma japonicum promoted the senescence of HSCs via STAT3/P53/P21 pathway. In this paper, our study was aimed to explore whether there are other signaling pathways in the process of SEA-induced HSCs aging and the underlying effect of SKP2/P27 signal on senescent HSCs.Methodology/Principal findingsHuman hepatic stellate cell line, LX-2 cells, were cultured and stimulated with SEA. Western blot and cellular immunofluorescence analysis were performed to determine the expression of senescence-associated protein, such as P27, SKP2 and FoxO3a. Besides, RNA interfering was applied to knockdown the expression of related protein. The senescence of HSCs was determined by senescence-associated β-gal staining. We found that SEA increased the expression of P27 protein, whereas it inhibited the expression of SKP2 and FoxO3a. Knockdown of P27 as well as overexpression of SKP2 both suppressed the SEA-induced senescence of HSCs. In addition, the nuclear translocation of FoxO3a from the nucleus to the cytoplasm was induced by SEA stimulation.Conclusions/SignificanceThe present study demonstrates that SEA promotes HSCs senescence through the FoxO3a/SKP2/P27 pathway.

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Section: Discussionmentioning

confidence: 99%

Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway

et al. 2016

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“…[61][62][63] Once p53 becomes activated by phosphorylation, [64][65][66][67] it upregulates its own transcription, creating a positive feedback loop, as well as another central checkpoint gene p21 (CDKN1A) which acts to inhibit various Cdks, leading to cell cycle arrest. [68][69][70][71][72][73] In parallel, p53 can also activate Bax in the apoptosis pathway promoting programmed cell death. [74][75][76][77] Although not the only gene responsible for cell cycle control, p53 is a central player in the regulation of cell cycle progression and its mutation in a variety of cancers demonstrates its essential protective function.…”

Section: Ehmt2 In Cell Cycle Regulationmentioning

confidence: 99%

The expanding role of the Ehmt2/G9a complex in neurodevelopment

2017

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Epigenetic regulators play a crucial role in neurodevelopment. One such epigenetic complex, Ehmt1/2 (G9a/GLP), is essential for repressing gene transcription by methylating H3K9 in a highly tissue-and temporal-specific manner. Recently, data has emerged suggesting that this complex plays additional roles in regulating the activity of numerous other non-histone proteins. While much is known about the downstream effects of Ehmt1/2 function, evidence is only beginning to come to light suggesting the control of Ehmt1/2 function may be, at least in part, due to context-dependent binding partners. Here we review emerging roles for the Ehmt1/2 complex suggesting that it may play a much larger role than previously recognized, and discuss binding partners that we and others have recently characterized which act to coordinate its activity during early neurodevelopment.

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“…Previous studies have suggested that the p53 gene serves an important role in the regulation of cell cycle progression (15)(16)(17). Therefore, the protein expression levels of p53 and its downstream target gene p21, as well as CDK2, cyclin A and cyclin E cell cycle mediators were investigated following exposure of eosinophils to 0, 80 or 160 µM resveratrol for 48 h. Western blot analysis demonstrated that the protein expression levels of p53 (P=0.0378; P=0.0085), and p21 (P=0.0327; P= 0.0054) were significantly increased following treatment with 80 and 160 µM resveratrol when compared with untreated controls (Fig.…”

Section: Resveratrol Induces Cell Cycle Arrest In Eosinophilsmentioning

confidence: 99%

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals

Hu¹,

Wang²,

Xia³

et al. 2016

Molecular Medicine Reports

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Abstract. Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit-8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double-staining. The protein expression levels of p53, p21, cyclin-dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration-and time-dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G 1 /S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl-2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

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The p53-p21-DREAM-CDE/CHR pathway regulates G₂/M cell cycle genes

Cited by 264 publications

References 61 publications

Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway

Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway

The expanding role of the Ehmt2/G9a complex in neurodevelopment

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals

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The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes

Cited by 264 publications

References 61 publications

Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway

Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway

The expanding role of the Ehmt2/G9a complex in neurodevelopment

Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals

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The p53-p21-DREAM-CDE/CHR pathway regulates G₂/M cell cycle genes