کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815385 | 1058471 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Insulin-induced cell division is controlled by the adaptor Grb14 in a Chfr-dependent manner
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 4, April 2015, Pages 798-806
Journal: Cellular Signalling - Volume 27, Issue 4, April 2015, Pages 798-806
نویسندگان
Dominique Perdereau, Katia Cailliau, Edith Browaeys-Poly, Arlette Lescuyer, Nadège Carré, Fadila Benhamed, Diana Goenaga, Anne-Françoise Burnol,