Title :

Insulin-induced cell division is controlled by the adaptor Grb14 in a Chfr-dependent manner

Author(s) :

Perdereau, Dominique [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]
Cailliau, Katia [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Laboratoire de Régulation des Signaux de Division
Browaeys-Poly, Edith [Auteur]
Laboratoire de Régulation des Signaux de Division
Lescuyer, Arlette [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Laboratoire de Régulation des Signaux de Division
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]

Journal title :

Cellular Signalling

Volume number :

27

Pages :

798-806

Publication date :

2015-04

ISSN :

0898-6568

English keyword(s) :

Cancer
Cell proliferation
Grb14
Insulin signalling

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Régulation des signaux de division

Submission date :

2020-02-12T15:44:30Z
2021-05-07T09:10:57Z