Downregulation of TAp63 and Unaffected Levels of p63? Distinguishes Oral Wounds from SCCHN

Thurfjell, Niklas; Coates, Philip J.; Wahlin, Ylva-Britt; Arvidsson, Elin; Nylander, Karin

doi:10.4161/cc.5.5.2496

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…24,25 ∆Np63 proteins are overexpressed in squamous cell carcinomas where they counteract TAp73 apoptotic capacity and contribute to the proliferative status of cancer cells. [26][27][28][29] ∆Np73 and ∆Np63 are transcribed from cryptic promoters localized in introns 3 of the respective genes. 30,11,31 While the regulation of ∆Np73 promoter has been extensively studied, the information concerning the regulation of ∆Np63 is still insufficient to depict a clear situation.…”

Section: Introductionmentioning

confidence: 99%

Cross-Talks in the p53 Family: ΔNp63 is an Anti-Apoptotic Target for ΔNp73α and p53 Gain of Function Mutants

Lanza¹,

Marinari²,

Papoutsaki³

et al. 2006

Cell Cycle

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The p53 family of transcription factors plays a pivotal role in the control of the cellular response to DNA damaging agents. In addition to pro-apoptotic molecules such as p53, TAp73 and TAp63, this gene family also encodes for the anti-apoptotic molecules deltaNp73, deltaNp63, deltaNp53, and p53 mutants are often found in tumor cells, that have the role to limit and to modulate the pro-apoptotic side of the family. The ratio between the different members of the family is critical to make the life or death decision following DNA damage and is tightly regulated by post-translational and transcriptional mechanisms. In this study we have uncovered a novel positive feedback that involves the transcriptional activation of the anti-apoptotic molecule deltaNp63 by the anti-apoptotic molecules deltaNp73 and mutant p53, and that is put into motion upon treatment with a subset of DNA damaging agents such as Doxorubicin and 5-FU. DeltaNp73 and mutant p53 associate with the deltaNp63 promoter inducing its transcription and this is enhanced by doxorubicin treatment. Furthermore we have observed that deltaNp73- and mutp53-mediated activation of the deltaNp63 promoter requires the functionality of the proximal CCAAT boxes of this promoter, being hampered by mutation of CCAAT boxes or by dominant negative NFYA expression. This mechanism may serve as an additional control of the response of a normal cell to DNA damage or as an anti-apoptotic barrier of cancer cells subjected to DNA damage.

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Section: Introductionmentioning

confidence: 99%

Cross-Talks in the p53 Family: ΔNp63 is an Anti-Apoptotic Target for ΔNp73α and p53 Gain of Function Mutants

Lanza¹,

Marinari²,

Papoutsaki³

et al. 2006

Cell Cycle

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“…ΔNp63 variants were found at high levels in basal and suprabasal keratinocytes of the hyperproliferative wound epithelium, TAp63 variants were also expressed in wound keratinocytes. Thurfjell et al [95] compared p63 status in normal oral wounds and in HNSCC, two situations that represent self-limiting and non-self-limiting processes. They found that both processes show upregulation of p63α and ΔNp63.…”

Section: Adhesion Migration Metastasis Invasivenessmentioning

confidence: 99%

The role of P63 in cancer, stem cells and cancer stem cells

Nekulova

Holcakova

Coates

et al. 2011

Cellular and Molecular Biology Letters

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The transcription factor p63 has important functions in tumorigenesis, epidermal differentiation and stem cell self-renewal. The TP63 gene encodes multiple protein isoforms that have different or even antagonistic roles in these processes. The balance of p63 isoforms, together with the presence or absence of the other p53 family members, p73 and p53, has a striking biological impact. There is increasing evidence that interactions between p53-family members, whether cooperative or antagonistic, are involved in various cell processes. This review summarizes the current understanding of the role of p63 in tumorigenesis, metastasis, cell migration and senescence. In particular, recent data indicate important roles in adult stem cell and cancer stem cell regulation and in the response of cancer cells to therapy.

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Molecular mechanisms of head and neck cancer

Deshpande

Wong²

2008

Expert Review of Anticancer Therapy

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Background-With a global incidence rank of eight and a significant portion of head and neck malignancies (~90%), oral squamous cell carcinoma (OSCC) poses a major health risk and is one of the leading cause of mortality in developing nations [1]. Distribution of the incidence of OSCC varies across the world with south-central Asia and Africa leading, followed by eastern and central Europe, and to a lesser extent Australia, Japan, and the United States. Over the past few years there has been a drastic increase in the incidence of oral cancer in most parts of the world [2]. In the United States alone, with about 17 new cases/100,000, oral cancer is the fifth most common and sixth leading cause of cancer-related mortality per year [3].While men tend to have a higher incidence of OSCC (6.6/100,000) compared to women (2.9/100,000), there is an equal mortality rate between the sexes (50%).

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Downregulation of TAp63 and Unaffected Levels of p63? Distinguishes Oral Wounds from SCCHN

Cited by 3 publications

References 14 publications

Cross-Talks in the p53 Family: ΔNp63 is an Anti-Apoptotic Target for ΔNp73α and p53 Gain of Function Mutants

Cross-Talks in the p53 Family: ΔNp63 is an Anti-Apoptotic Target for ΔNp73α and p53 Gain of Function Mutants

The role of P63 in cancer, stem cells and cancer stem cells

Molecular mechanisms of head and neck cancer

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