The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

Vilborg, Anna; Bersani, Cinzia; Wilhelm, Margareta; Wiman, Klas G.

doi:10.1038/cdd.2011.20

Cited by 29 publications

(30 citation statements)

References 65 publications

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“…WIG-1 as a bona fide p53 target gene has been confirmed by a number of studies [15,17,19] and is further supported by microarray data showing WIG-1 upregulation after p53 activation by the small molecule RITA [20]. However, it is clear that p53 is not the only transcription factor that regulates WIG-1 expression, as WIG-1 is expressed at robust levels also in cells lacking p53 [21]. Our results also suggested that zinc could upregulate the expression of WIG-1 not by regulating the p53.…”

Section: Discussionmentioning

confidence: 74%

Zinc induces cell cycle arrest and apoptosis by upregulation of WIG-1 in esophageal squamous cancer cell line EC109

et al. 2011

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Zinc deficiency was implicated in the etiologies of human esophageal squamous cell carcinoma (ESCC). Wild-type p53-induced gene 1 (WIG-1), a kind of zinc finger protein, was cloned from the human 3q26.3 region and encoded a putative polypeptide of 289 amino acids. Our previous studies have demonstrated that the expression of WIG-1 was downregulated in ESCC tissues. Herein, we investigated the effect of zinc on cell proliferation, apoptosis, as well as expression of WIG-1 in EC109 cells. Meanwhile, an RNAi vector of WIG-1 was transfected into EC109 cells and the effect of zinc on WIG-1 expression was investigated. We found that zinc could suppress cell proliferation and induce G0/G1 cell cycle arrest and apoptosis of EC109, and this efficacy might result from the expression altering of several apoptosis-related genes, such as Bax, p21 ( WAF ), and cyclin D1. In particular, upregulation of WIG-1 was observed after zinc supplementation, indicating that WIG-1 might be involved in the zinc-induced cell cycle arrest and apoptosis of EC109 cells by regulating the expression of Bax, p21 ( WAF ), and cyclin D1.

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Section: Discussionmentioning

confidence: 74%

Zinc induces cell cycle arrest and apoptosis by upregulation of WIG-1 in esophageal squamous cancer cell line EC109

et al. 2011

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“…Later studies demonstrated the ability of ZMAT3 to bind to double stranded RNA, besides DNA, and is thought to play a role similar to that of miRNA [87-89]. Interestingly, its expression was found to be highest in the brain [89].…”

Section: Discussionmentioning

confidence: 99%

Sporadic Alzheimer disease fibroblasts display an oxidative stress phenotype

Ramamoorthy

Sýkora

Scheibye‐Knudsen

et al. 2012

Free Radical Biology and Medicine

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Alzheimer's disease (AD) is a major health problem in the US, affecting one in eight Americans over the age of 65. The number of elderly suffering from AD is expected to continue to increase over the next decade, as the average age of the US population increases. The risk factors for and etiology of AD are not well understood; however, recent studies suggest that exposure to oxidative stress may be a contributing factor. Here, microarray gene expression signatures were compared in AD patient-derived fibroblasts and normal fibroblasts exposed to hydrogen peroxide or menadione (to simulate conditions of oxidative stress). Using the 23K Illumina cDNA microarray to screen expression of > 14,000 human genes, we identified a total of 1017 genes that are chronically up- or down-regulated in AD fibroblasts, 215 of which were also differentially expressed in normal human fibroblasts within 12 h after exposure to hydrogen peroxide or menadione. Pathway analysis of these 215 genes and their associated pathways reveals cellular functions that may be critically dysregulated by oxidative stress and play a critical role in the etiology and/or pathology of AD. We then examined the AD fibroblasts for the presence of oxidative DNA damage and found increased accumulation of 8-oxo-guanine. These results indicate the possible role of oxidative stress in the gene expression profile seen in AD.

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“…A reduction in p53 increases cell reprogramming efficacy and facilitates induced pluripotent stem cell (iPSC) generation [137]. p53 may also act to regulate stem cell fate by targeting a variety of factors, such as Wig1, a transcriptional p53 target encoding a zinc-finger protein involved in post-transcriptional gene regulation, and is found to be highly expressed in stem cells [151]. In tumors, mut p53 acquires GOF processes to influence stemness as observed in its ability to stimulate iPSC formation while augmenting the malignant potential of reprogrammed cells [20].…”

Section: P53 and Stem Cellsmentioning

confidence: 99%

Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness

Olivos

Mayo

2016

IJMS

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Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53’s functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche. We will also examine p53 gain of function (GOF) roles in stemness. Mutant p53 (mutp53) GOFs that lead to survival, drug resistance and colonization are reviewed in the context of the acquisition of advantageous transformation processes, such as differentiation and dedifferentiation, epithelial-to-mesenchymal transition (EMT) and stem cell senescence and quiescence. Finally, we will conclude with therapeutic strategies that restore wild-type p53 (wtp53) function in cancer and CSCs, including RING finger E3 ligases and CSC maintenance. The mechanisms by which wtp53 and mutp53 influence stemness in non-malignant stem cells and CSCs or tumor-initiating cells (TICs) are poorly understood thus far. Further elucidation of p53’s effects on stemness could lead to novel therapeutic strategies in cancer research.

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The p53 target Wig-1: a regulator of mRNA stability and stem cell fate?

Cited by 29 publications

References 65 publications

Zinc induces cell cycle arrest and apoptosis by upregulation of WIG-1 in esophageal squamous cancer cell line EC109

Zinc induces cell cycle arrest and apoptosis by upregulation of WIG-1 in esophageal squamous cancer cell line EC109

Sporadic Alzheimer disease fibroblasts display an oxidative stress phenotype

Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness

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