HIF-1α and p53: the ODD couple?

Fels, Diane; Koumenis, Constantinos

doi:10.1016/j.tibs.2005.06.009

Cited by 61 publications

(52 citation statements)

References 29 publications

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“…It is well known that the Mdm2 oncogene negatively regulates a tumor suppressor p53, and that the tumor suppressor pVHL negatively regulates the oncogene-like HIF. Moreover, it has also been reported that p53 is a negative regulator of HIF, 31 and that Mdm2 (Hdm2) is a positive regulator of HIF-1α. 32 In a recent study, we also demonstrated that pVHL positively regulates p53.…”

Section: Discussionmentioning

confidence: 99%

The Positive Regulation of p53 by the Tumor Suppressor VHL

Roe

Youn²

2006

Cell Cycle

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Section: Discussionmentioning

confidence: 99%

The Positive Regulation of p53 by the Tumor Suppressor VHL

Roe

Youn²

2006

Cell Cycle

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“…Moreover, numerous studies provide in vitro evidence supporting a direct interaction between p53 and HIF (Fels and Koumenis, 2005). The array data indicated that tp53 was induced in Hx and further induced when fih was silenced (Table 1).…”

Section: Fih Controls In Vitro P53 Expressionmentioning

confidence: 96%

The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression of the p53–p21 axis

et al. 2011

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We showed previously that factor-inhibiting hypoxiainducible factor HIF (FIH) monitors the expression of a spectrum of genes that are dictated by the cell's partial oxygen pressure. This action is mediated by the C-TAD, one of two transactivation domains (TADs) of the hypoxia-inducible factor. Here, we questioned: (1) the function of FIH as a HIF-1 modulator of gene expression in the context of a physiological oxygen gradient occurring in three-dimensional cultures and in tumors and (2) the role of FIH as a modulator of the growth of human tumor cells. We first showed that the expression pattern of HIF target genes that depend on the C-TAD, such as carbonic anhydrase IX, was spacially displaced to more oxygenated areas when FIH was silenced, whereas overexpression of FIH restricted this pattern to more hypoxic areas. Second, we showed that silencing fih severely reduced in vitro cell proliferation and in vivo tumor growth of LS174 colon adenocarcinoma and A375 melanoma cells. Finally, silencing of fih significantly increased both the total and phosphorylated forms of the tumor suppressor p53, leading to an increase in its direct target, the cell cycle inhibitor p21. Moreover, p53-deficient or mutant cells were totally insensitive to FIH expression. Thus, FIH activity is essential for tumor growth through the suppression of the p53-p21 axis, the major barrier that prevents cancer progression.

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“…HPV-16 E6 and E7 proteins increase the secretion of proangiogenic factors, VEGF and IL-8, and downregulate the expression of negative regulators of angiogenesis such as TSP-1, maspin, a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), plasminogen activator and fibronectin 1. Among these genes, TSP-1, maspin and VEGF have also been shown to be regulated by p53 (Ravi et al, 2000;Zou et al, 2000;Harada et al, 2003), whose role in the angiogenic process has been clearly described (Bergers and Benjamin, 2003;Fels and Koumenis, 2005). However, the HPV-16 E7 but not E6 protein strongly enhances the release of angiogenic factors tumor necrosis factor-a (TNF-a), IL-1b and IL-6 by activated macrophages (Le Buanec et al, 1999).…”

Section: Modulation Of Angiogenesis By Oncoviral Proteins Targeting Rmentioning

confidence: 99%

Involvement of RB gene family in tumor angiogenesis

Gabellini¹,

Bufalo²,

Zupi³

2006

Oncogene

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Angiogenesis, the development of new blood vessels from pre-existing vessels, represents a fundamental step in tumor progression and metastatization. The induction of vasculature is required for growth of the tumor mass, to ensure an adequate supply of oxygen and metabolites to the tumor beyond a critical size. Tumor angiogenesis is a highly regulated process that is controlled physiologically by the tumor microenvironment and genetically by alteration of several oncogenes or tumor suppressor genes. We will focus on recent demonstrations regarding the involvement of the retinoblastoma family proteins (phosphorylated retinoblastoma (pRb), p107 and pRb2/p130) at different levels of the angiogenic process. pRb and its homologs can regulate the expression of pro-and antiangiogenic factors, such as the vascular endothelial growth factor, through an E2F-dependent mechanism. Moreover, pRb is able to modulate also the transcriptional activity of several angiogenesis-related factors like HIF-1, Id2 and Oct-1. pRb2/p130 is required for both differentiation and mobilization of bone marrow-derived endothelial cell precursors and endothelial sprouting from neighboring vessels. The involvement of the pRb pathway in the angiogenesis process has also been demonstrated by different cellular models expressing viral oncoproteins, like human papilloma virus. Moreover, some natural and synthetic compounds demonstrate their antiangiogenetic activity with a mechanism of action involving pRb. Finally, the possible prognostic value of immunohistochemical evaluation of pRb and/or pRb2/p130 expression can represent a useful tool for the characterization of the angiogenic phenotype of specific tumor histotypes.

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HIF-1α and p53: the ODD couple?

Cited by 61 publications

References 29 publications

The Positive Regulation of p53 by the Tumor Suppressor VHL

The Positive Regulation of p53 by the Tumor Suppressor VHL

The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression of the p53–p21 axis

Involvement of RB gene family in tumor angiogenesis

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