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Coopération entre les isoformes TAp73 et la signalisation TGF-β dans la régulation de l'expression de la NO Synthase inductible

Abstract : Nitric oxide (NO) is a gaseous molecule synthesized from L-arginine by Nitric Oxide Synthases. NO acts as a potent signaling molecule in various physiological processes like vasorelaxation and neurotransmission. It modulates the activity of many proteins (e.g. soluble guanylate cyclase and ribonucleotide reductase) through nitrosylation of thiol moieties or transition metal ions. As a free radical, NO can also react with a number of cellular species, notably molecular oxygen, to form reactive oxygen species and reactive nitrogen species. Thanks to these properties, NO appears as a major component of innate immune response and inflammation. Phagocytes produce large amounts of NO in response to proinflammatory through inducible Nitric Oxide Synthase (iNOS) activity. Because of the harmful effects of NO derivatives on cellular components, iNOS activity needs to be tightly regulated. The p53 tumor suppressor has been shown to repress Nos2 after being activated by NO itself. The p73 protein is an homologous encoded by the TP73 gene that generate transcriptionally active TAp73 isoforms and ΔNp73 isoforms that lack the transactivation domain and exert a dominant negative effect. This study focuses on the role of TAp73 isoforms in regulation of iNOS expression. We demonstrate that TAp73 isoforms potentiate the repressive effect of TGF-β on iNOS expression at transcriptional and post-traductional levels, resulting in a substantial iNOS overexpression in TAp73-/- cells. These results emphasize the emerging role of p53 family as a master regulator of TGF-β functions.
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Submitted on : Wednesday, January 2, 2019 - 1:09:08 AM
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  • HAL Id : tel-01968024, version 1


Aimeric Cabrié. Coopération entre les isoformes TAp73 et la signalisation TGF-β dans la régulation de l'expression de la NO Synthase inductible. Immunité innée. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS397⟩. ⟨tel-01968024⟩



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