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O ‐glycosylation of FoxO1 increases its transcriptional activity towards the glucose 6‐phosphatase gene
Author(s) -
Kuo MeiShiue,
Zilberfarb Vladimir,
Gangneux Nicolas,
Christeff Névéna,
Issad Tarik
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.010
Subject(s) - foxo1 , glycosylation , phosphatase , chemistry , glucosamine , mutant , reporter gene , downregulation and upregulation , gene , glucose 6 phosphatase , gene expression , biochemistry , microbiology and biotechnology , enzyme , biology , transcription factor
Mono‐ O ‐glycosylations post‐translationally regulate the activity of nucleocytoplasmic proteins. We showed that glucosamine and an inhibitor of deglycosylation (PUGNAc) induced O ‐glycosylation of FoxO1, resulting in increased expression of a glucose‐6‐phosphatase reporter gene. This effect was independent of FoxO1 re‐localisation, since it was also observed with constitutively nuclear FoxO1‐AAA mutant. Moreover, in HepG2 cells, glucosamine and PUGNAc have a synergistic effect on the glucose‐6‐phosphatase reporter gene, and this effect was inhibited by FoxO1 siRNAs. Since glucose‐6‐phosphatase plays a key role in hepatic glucose production, our observation may be of importance with regard to glucotoxicity associated with chronic hyperglycaemia in diabetes.