DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.

Valérie Glorian; Jennifer Allègre; Jean Berthelet; Baptiste Dumetier; Pierre-Marie Boutanquoi; Nathalie Droin; Cémile Kayaci; Jessy Cartier; Simon Gemble; Guillaume Marcion; Daniel Gonzalez; Romain Boidot; Carmen Garrido; Olivier Michaud; Eric Solary; Laurence Dubrez

doi:10.1038/cddis.2017.222

DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.

Valérie Glorian ¹ Jennifer Allègre ¹ Jean Berthelet ¹ Baptiste Dumetier ¹ Pierre-Marie Boutanquoi ¹ Nathalie Droin ² Cémile Kayaci ¹ Jessy Cartier ¹ Simon Gemble ¹ Guillaume Marcion ¹ Daniel Gonzalez ^{3, 1} Romain Boidot ^{3, 1} Carmen Garrido ¹ Olivier Michaud ¹ Eric Solary ^{2, 4} Laurence Dubrez ^{1, *}

* Auteur correspondant

1 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]

2 U1170 Inserm - Hématopoïèse normale et pathologique

3 CRLCC - CGFL - Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc

4 Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre

Abstract : The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control. Importantly, E2F1 stabilization in response to etoposide-induced DNA damage or during the S phase of cell cycle, as revealed by cyclin A silencing, is associated with K63-poly-ubiquitinylation of E2F1 on lysine 161/164 residues and involves cIAP1. Our results reveal an additional level of regulation of the stability and the activity of E2F1 by a non-degradative K63-poly-ubiquitination and uncover a novel function for the E3-ubiquitin ligase cIAP1.

Keywords : polysialic acid hypothalamus atherosclerosis LDL HDL synaptic plasticity

Type de document :

Article dans une revue

Cell Death and Disease , Nature Publishing Group, 2017, 8 (5), pp.e2816. 〈http://www.nature.com/cddis/journal/v8/n5/full/cddis2017222a.html?foxtrotcallback=true〉. 〈10.1038/cddis.2017.222〉

Domaine :

Sciences du Vivant [q-bio] / Médecine humaine et pathologie

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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01542105
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : lundi 19 juin 2017 - 15:29:31
Dernière modification le : jeudi 11 octobre 2018 - 17:06:01

Valérie Glorian, Jennifer Allègre, Jean Berthelet, Baptiste Dumetier, Pierre-Marie Boutanquoi, et al.. DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.. Cell Death and Disease , Nature Publishing Group, 2017, 8 (5), pp.e2816. 〈http://www.nature.com/cddis/journal/v8/n5/full/cddis2017222a.html?foxtrotcallback=true〉. 〈10.1038/cddis.2017.222〉. 〈hal-01542105〉

DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.

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DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.

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