Related Experiment Video
Updated: Jun 13, 2025

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid
Carla E Cadena Del Castillo1, Onur Deniz2, Femke van Geest1
1Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
Abstract:
The heterodimeric ChREBP-MLX transcription factor complex is a key mediator that couples intracellular sugar levels to carbohydrate and lipid metabolism. To promote the expression of target genes, two ChREBP-MLX heterodimers form a heterotetramer to bind a tandem element with two adjacent E-boxes, called Carbohydrate Responsive Element (ChoRE). How the ChREBP-MLX hetero-tetramerization is achieved and regulated, remains poorly understood. Here we show that MLX phosphorylation on an evolutionarily conserved motif is necessary for the heterotetramer formation on the ChoRE and the transcriptional activity of the ChREBP-MLX complex. We identified CK2 and GSK3 as MLX kinases that coordinately phosphorylate MLX. High intracellular glucose-6-phosphate accumulation inhibits MLX phosphorylation and heterotetramer formation on the ChoRE, impairing ChREBP-MLX activity. Physiologically, MLX phosphorylation is necessary in Drosophila to maintain sugar tolerance and lipid homeostasis. Our findings suggest that MLX phosphorylation is a key mechanism for the ChREBP-MLX heterotetramer formation to regulate carbohydrate and lipid metabolism.
Related Concept Videos
Master Transcription Regulators
Cell Specific Gene Expression
cAMP-dependent Protein Kinase Pathways
Regulation of Metabolism
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Chromatin Structure Regulates pre-mRNA Processing
The chromatin structure, especially...

