Role of NF-kB, p53, and p21 in the Regulation of TNF-α Mediated Apoptosis of Lymphocytes

Ryazantseva, N. V.; Новицкий, В. В.; Жукова, О. Б.; Biktasova, Asel; Чечина, О. Е.; Sazonova, Elena V.; Radzivil, T. T.; Wice, A. N.; Chasovskikh, N. Yu.

doi:10.1007/s10517-010-0873-8

Cited by 18 publications

(11 citation statements)

References 10 publications

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“…For diVerent types of cells and in response to diVerent stimuli, p53 is regulated by transcription factors, such as NF-B, AP-1, and STAT (Ho and Ames 2002;Ryazantseva et al 2010). In a previous study, we found a signal pathway that inhibits p53 function through NF-B/mot-2 in HELF cells .…”

Section: Discussionmentioning

confidence: 84%

Blockade of p53 by HIF-2α, but not HIF-1α, is involved in arsenite-induced malignant transformation of human bronchial epithelial cells

Pang

et al. 2012

Arch Toxicol

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Hypoxia-inducible factors (HIFs), which consist of α and β subunits, are transcription factors involved in regulation of a variety of cellular functions. By blocking the function of the tumor suppressor p53, over-expressions of HIFs are linked to carcinogenesis and tumor progression. Inorganic arsenic, a ubiquitous environmental contaminant, is associated with an increased risk of cancer. Although there are several hypotheses regarding arsenic-induced carcinogenesis, the mechanism of action remains obscure. We have shown that long-term exposure of human bronchial epithelial (HBE) cells to a low level of arsenite increases their proliferation rate and anchorage-independent growth. When introduced into nude mice, the transformed cells are tumorigenic. The present report demonstrates that, with increased time of exposure to arsenite, there is more increased expression of HIF-2α, but not HIF-1α. These factors are known to have different functions, and, in some cases, opposite effects. Arsenite induces accumulation of HIF-2α by inhibiting its degradation through the ubiquitin-mediated proteasome pathway. HIF-2α knockdown, but not HIF-1α knockdown, increases the activation of p53. Finally, inhibition of HIF-2α blocks arsenite-induced proliferation and malignant transformation. Thus, our studies show that blockade of p53 function by inhibiting the ubiquitin-mediated proteasome degradation of HIF-2α, but not that of HIF-1α, is involved in arsenite-induced proliferation and neoplastic transformation of HBE cells.

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Section: Discussionmentioning

confidence: 84%

Blockade of p53 by HIF-2α, but not HIF-1α, is involved in arsenite-induced malignant transformation of human bronchial epithelial cells

Pang

et al. 2012

Arch Toxicol

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“…These complexes block the cell-cycle transition from the G1 phase to the S phase. P21 is regulated by two different pathways, i.e., a p53-dependent pathway (DNA damage leading to the activation of p53 and upregulation of p21 causing cell cycle blockage in the G1 phase with possible DNA repair or induction of apoptosis), and a p53-independent pathway (through cell growth factors, such as interferon-β and tumor necrosis factor-α, which are able to induce p21 in p53-deficient cells in quiescence) [ 25 , 26 ]. Our results also indicated that p21 overexpression was connected with the depression of CDK 2 and cyclinE in human RPE cells, leading to arrest of the cell cycle and reduction of the proliferation of cells.…”

Section: Discussionmentioning

confidence: 99%

Overexpression p21WAF1/CIP1 in suppressing retinal pigment epithelial cells and progression of proliferative vitreoretinopathy via inhibition CDK2 and cyclin E

et al. 2014

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BackgroundP21 is one kind of cyclin-dependent kinase inhibitor that can prevent cells from going through the G1/S phase checkpoint and inhibit cell proliferation. Proliferative vitreoretinopathy (PVR) is a proliferative response in the eye. The aim of this study was to determine whether p21Waf1/Cip1 (p21) suppresses the proliferation and migration of retinal pigment epithelial (RPE) cells in vitro and controls PVR development in vivo.MethodsCell cycle analyses and transwell assays were conducted to assess cell proliferation characteristics and the migration ability of RPE cells after transfection with p21. Western blot and reverse-transcription polymerase chain reaction technologies were used to detect the expression of p21, CDK2 and cyclinE in RPE cells and rabbit retinal tissues. The impact of increasing p21 expression on PVR development was conducted by implantation of an adenovirus vector containing rabbit p21 (rAd-p21) in a PVR rabbit model. The prevalence of PVR and retinal detachment was determined by indirect ophthalmoscopy on days 3, 7, 14, and 21 after the injection of rAd-p21 into the vitreous. B scans and hematoxylin-eosin staining were employed to check rabbit retinas on day 21.ResultsCell cycle analyses and transwell assays showed that p21 inhibited the proliferation and migration of RPE cells. Increased expression of p21 was detected in cultured RPE cells and rabbit retinas after transfection with the p21 gene, whereas levels of CDK2 and cyclinE were decreased. The increase in p21 expression effectively suppressed the development of PVR in a rabbit model.ConclusionsThe increase in p21 expression in RPE cells not only inhibits the proliferation and migration of RPE cells in vitro, but also suppresses the development of PVR in vivo, which indicates its therapeutic potential in treating PVR.

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“…Mitogen activation of human primary lymphocytes in vitro results in an increase in both TNF and CDKN1A mRNA levels, whereas treatment with the immunosuppressant cyclosporin, which inhibits T lymphocyte proliferation, reduces TNF mRNA levels but increases expression of CDKN1A both at the level of mRNA and protein (Khanna 2005). Treatment of human PBMC with TNF in vitro increases apoptosis and necrosis via a process that involves increases in levels of CDKN1A protein (Ryazantseva et al 2010). TNF has also been shown to stimulate CDKN1A expression, both at the level of mRNA and protein in murine alveolar cells and macrophages, while CDKN1A can suppress TGF-b induced TNF expression (Yamasaki et al 2008).…”

Section: Effects Of Extended Fast On Pbmc Transcription Profilesmentioning

confidence: 99%

Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism

et al. 2014

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Role of NF-kB, p53, and p21 in the Regulation of TNF-α Mediated Apoptosis of Lymphocytes

Cited by 18 publications

References 10 publications

Blockade of p53 by HIF-2α, but not HIF-1α, is involved in arsenite-induced malignant transformation of human bronchial epithelial cells

Blockade of p53 by HIF-2α, but not HIF-1α, is involved in arsenite-induced malignant transformation of human bronchial epithelial cells

Overexpression p21WAF1/CIP1 in suppressing retinal pigment epithelial cells and progression of proliferative vitreoretinopathy via inhibition CDK2 and cyclin E

Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism

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