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La protéine ING2 : Nouvelles fonctions suppressives de tumeurs et régulation par sumoylation.

Abstract : ING tumor suppressor genes family (ING1-5) was identified between 1996 and 2001 and was shown to repress cell proliferation by regulating cell cycle progression, apoptosis and/or senescence in a p53 dependent manner, when overexpressed. The founding member of the family, ING1, has been described as frequently inactivated in many human cancer types. Moreover ING1 KO mice develop tumors earlier and more frequently, indicating a role for ING1 in tumor suppression. Although ING1 has received much attention, limited information on the status and functions of the other members of the family are available. In this context, I have studied ING2 member of the ING family having the highest homology to ING1, in order to determine its potential tumor suppressive role in human cancers. To address this question we have first determined its status in human lung tumor biopsies and have shown that its expression is lost (both at protein and mRNA levels) in more than half of the 120 tumors screened. Concomitantly, we have looked for ING2 relevant functions that may contribute to tumor development when inactivated. Indeed, we have shown that ING2 knock-down induces replication defects and increases genome instability. In the mean time, we have shown that ING2 can be posttranslationally modified by sumoylation which is critical for ING2 association with the Sin3A chromatin remodeling complex to regulate gene expression. Overall, these studies have contributed to comfort ING2 involvement in tumorigenesis and have highlighted new functions that document how ING proteins inactivation may contribute to cancer development.
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https://tel.archives-ouvertes.fr/tel-00448002
Contributor : Damien Ythier <>
Submitted on : Monday, January 18, 2010 - 10:51:20 AM
Last modification on : Friday, November 6, 2020 - 4:03:42 AM
Long-term archiving on: : Thursday, June 17, 2010 - 10:53:52 PM

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  • HAL Id : tel-00448002, version 1

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Damien Ythier. La protéine ING2 : Nouvelles fonctions suppressives de tumeurs et régulation par sumoylation.. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00448002⟩

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