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Hypoxia‐inducible factor independent down‐regulation of thioredoxin‐interacting protein in hypoxia
Author(s) -
Chai Tin Fan,
Leck Yee Chin,
He Hongpeng,
Yu Fa-Xing,
Luo Yan,
Hagen Thilo
Publication year - 2011
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.2010.12.033
Subject(s) - txnip , thioredoxin interacting protein , carbohydrate responsive element binding protein , glycolysis , hypoxia (environmental) , chemistry , transcription factor , carbohydrate metabolism , hypoxia inducible factors , microbiology and biotechnology , biochemistry , thioredoxin , metabolism , biology , oxygen , gene , organic chemistry
Thioredoxin‐Interacting Protein (Txnip) is an important regulator of glucose metabolism and functions by inhibiting cellular glucose uptake. The expression of the Txnip gene is sensitive to glucose availability and is negatively correlated with the glycolytic rate. Here we show that hypoxia induces a rapid decrease in Txnip mRNA and protein expression in a Hypoxia‐Inducible Factor independent manner. Hypoxia caused reduced binding of the glucose responsive MondoA:Mlx transcription factor to the carbohydrate response elements (ChoREs) in the Txnip promoter. Our data suggest that hypoxia decreases MondoA:Mlx activity by increasing glycolytic flux, leading to the depletion of glycolytic intermediates which normally activate MondoA:Mlx. Hypoxia dependent Txnip down‐regulation may be an important compensatory mechanism through which cancer cells adapt their metabolism to low oxygen concentrations.