Glucose-6-Phosphate Upregulates Txnip Expression by Interacting With MondoA

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2020 Jan 30

PMID 31993438

Citations 4

Authors

Xueyun Zhang

Tao Fu

Qian He

Xiang Gao

Yan Luo

Affiliations

Soon will be listed here.

Abstract

The major metabolic fates of glucose in cells are glycolysis and the pentose phosphate pathway, and they share the first step: converting glucose to glucose-6-phosphate (G6P). Here, we show that G6P can be sensed by the transcription factor MondoA/Mlx to modulate Txnip expression. Endogenous knockdown and EMSA (gel migration assay) analyses both confirmed that G6P is the metabolic intermediate that activates the heterocomplex MondoA/Mlx to elicit the expression of Txnip. Additionally, the three-dimensional structure of MondoA is modeled, and the binding mode of G6P to MondoA is also predicted by molecular docking and binding free energy calculation. Finally, free energy decomposition and mutational analyses suggest that certain residues in MondoA, GKL139-141 in particular, mediate its binding with G6P to activate MondoA, which signals the upregulation of the expression of Txnip.

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