Project : Study of O-GlcNAc glycosylation of FoxO1 the betapancreatic Cell
O-GlcNAc glycosylation of cytosolic and nuclear proteins constitutes a reversible post-translational modification, analogous to phosphorylation, which now appears as a major player in the regulation of cell signalling. This modification depends on glucose concentrations, allowing a regulation of protein activities according to the metabolic environment of the cell. O-GlcNAc modification could therefore participate in the deleterious effects associated with chronic
hyperglycaemia observed in diabetes (glucotoxicty).
The transcription factor FoxO1 plays a major role in important biological processes such as regulation of energy metabolism as well as cell proliferation and apoptosis, notably in pancreatic beta-cells.
Our team was the first to demonstrate that FoxO1 is O-Glycosylated, resulting in an increase in its transcriptional activity in liver cells. More recently, we have observed that FoxO1 is also O-glycosylated in pancreatic beta-cells. This mechanism could play a crucial role in pancreatic glucotoxicity, by inducing the apoptosis of the beta cells.
The objective of this project will be to determine the consequences of O-GlcNAc glycosylation of FoxO1 in pancreatic beta-cells. The project involves the use of betapancreatic cell lines, isolated pancreatic islets as well as inducible FoxO1 KO animals.
Please send by E-mail, CV, motivation letter, list of publications and names, E-mail addresses, and telephone n° of 3 references at: Dr. Tarik ISSAD, Institut Cochin, Departement of Endocrinology, Metabolism and Cancer Team « Glucose and insulin signalling, and Glucotoxicity »
E-mail: tarik.issad@ inserm.fr
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