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Hsp70 est un nouveau régulateur majeur de l'érythropoïèse empêchant le clivage du facteur de transcription GATA-1 par la caspase-3 au cours de la différenciation.

Abstract : Red blood cells production depends on apoptosis rate of erythroid precursors. This process is mainly regulated by the erythropoietin (Epo). Thus, Epo starvation results in caspase-3 (casp-3) activation and as a consequence GATA-1 is cleaved and apoptosis of immature erythroblasts occurs. Casp-3 activation is also absolutely required for the morphological changes that occur during normal human terminal erythroid differentiation. In this context, although that caspase-3 is activated, apoptosis and GATA-1 cleavage do not occur. The aim of this thesis, was to study if the inducible form of Hsp70 which is chaperon protein that play a major role as a modulator of apoptosis. Here, we show that inducible Hsp70 is constituvely expressed during human terminal erythroid differentiation, in both nuclear and cytoplasmic erythroblast compartments. Hsp70 and co-localizes with GATA-1 in the nucleus at the onset of caspases activation during terminal erythroid differentiation. Hsp70 nuclear localization is regulated by Epo: after Epo starvation, while Hsp70 nuclear localization is lost, GATA-1 is cleaved. Transfection of siRNA Hsp70, reduces significantly Hsp 70 expression, and is associated with GATA-1 cleavage at the onset of casp-3 activation occuring during erythroid differentiation. Hsp70 inhibition leads to stop differentiation and increase cell death. Therefore, Hsp70 exerts a new critical anti-apoptotic role during terminal erythropoiesis. We propose a model in which, Epo determines the fate of erythroblasts (apoptosis vs. differentiation) downstream of casp-3 activation by regulating the nuclear localization of Hsp70.
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https://tel.archives-ouvertes.fr/tel-00451047
Contributor : Catherine Slama <>
Submitted on : Thursday, January 28, 2010 - 9:49:40 AM
Last modification on : Friday, October 23, 2020 - 4:45:00 PM
Long-term archiving on: : Wednesday, November 30, 2016 - 11:44:56 AM

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  • HAL Id : tel-00451047, version 1

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Jean-Antoine Ribeil. Hsp70 est un nouveau régulateur majeur de l'érythropoïèse empêchant le clivage du facteur de transcription GATA-1 par la caspase-3 au cours de la différenciation.. Sciences du Vivant [q-bio]. Université Paris-Diderot - Paris VII, 2010. Français. ⟨tel-00451047⟩

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