Insulin-induced cell division is controlled ...
Type de document :
Article dans une revue scientifique
URL permanente :
Titre :
Insulin-induced cell division is controlled by the adaptor Grb14 in a Chfr-dependent manner
Auteur(s) :
Perdereau, Dominique [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Cailliau, Katia [Auteur]
Laboratoire de Régulation des Signaux de Division
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Browaeys-Poly, Edith [Auteur]
Laboratoire de Régulation des Signaux de Division
Lescuyer, Arlette [Auteur]
Laboratoire de Régulation des Signaux de Division
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Carré, Nadège [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Benhamed, Fadila [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Goenaga, Diana [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Burnol, Anne-Françoise [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Institut Cochin [UMR_S567 / UMR 8104]
Cailliau, Katia [Auteur]
Laboratoire de Régulation des Signaux de Division
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Browaeys-Poly, Edith [Auteur]
Laboratoire de Régulation des Signaux de Division
Lescuyer, Arlette [Auteur]
Laboratoire de Régulation des Signaux de Division
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Carré, Nadège [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Benhamed, Fadila [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Goenaga, Diana [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Burnol, Anne-Françoise [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Titre de la revue :
Cellular Signalling
Numéro :
27
Pagination :
798-806
Date de publication :
2015-04
ISSN :
0898-6568
Mot(s)-clé(s) en anglais :
Cancer
Cell proliferation
Grb14
Insulin signalling
Cell proliferation
Grb14
Insulin signalling
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
Beyond its key role in the control of energy metabolism, insulin is also an important regulator of cell division and neoplasia. However, the molecular events involved in insulin-driven cell proliferation are not fully ...
Lire la suite >Beyond its key role in the control of energy metabolism, insulin is also an important regulator of cell division and neoplasia. However, the molecular events involved in insulin-driven cell proliferation are not fully elucidated. Here, we show that the ubiquitin ligase Chfr, a checkpoint protein involved in G2/M transition, is a new effector involved in the control of insulin-induced cell proliferation. Chfr is identified as a partner of the molecular adapter Grb14, an inhibitor of insulin signalling. Using mammalian cell lines and the Xenopus oocyte as a model of G2/M transition, we demonstrate that Chfr potentiates the inhibitory effect of Grb14 on insulin-induced cell division. Insulin stimulates Chfr binding to the T220 residue of Grb14. Both Chfr binding site and Grb14 C-ter BPS-SH2 domain, mediating IR binding and inhibition, are required to prevent insulin-induced cell division. Targeted mutagenesis revealed that Chfr ligase activity and phosphorylation of its T39 residue, a target of Akt, are required to potentiate Grb14 inhibitory activity. In the presence of insulin, the binding of Chfr to Grb14 activates its ligase activity, leading to Aurora A and Polo-like kinase degradation and blocking cell division. Collectively, our results show that Chfr and Grb14 collaborate in a negative feedback loop controlling insulin-stimulated cell division.Lire moins >
Lire la suite >Beyond its key role in the control of energy metabolism, insulin is also an important regulator of cell division and neoplasia. However, the molecular events involved in insulin-driven cell proliferation are not fully elucidated. Here, we show that the ubiquitin ligase Chfr, a checkpoint protein involved in G2/M transition, is a new effector involved in the control of insulin-induced cell proliferation. Chfr is identified as a partner of the molecular adapter Grb14, an inhibitor of insulin signalling. Using mammalian cell lines and the Xenopus oocyte as a model of G2/M transition, we demonstrate that Chfr potentiates the inhibitory effect of Grb14 on insulin-induced cell division. Insulin stimulates Chfr binding to the T220 residue of Grb14. Both Chfr binding site and Grb14 C-ter BPS-SH2 domain, mediating IR binding and inhibition, are required to prevent insulin-induced cell division. Targeted mutagenesis revealed that Chfr ligase activity and phosphorylation of its T39 residue, a target of Akt, are required to potentiate Grb14 inhibitory activity. In the presence of insulin, the binding of Chfr to Grb14 activates its ligase activity, leading to Aurora A and Polo-like kinase degradation and blocking cell division. Collectively, our results show that Chfr and Grb14 collaborate in a negative feedback loop controlling insulin-stimulated cell division.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
Régulation des signaux de division
Date de dépôt :
2020-02-12T15:44:30Z
2021-05-07T09:10:57Z
2021-05-07T09:10:57Z