MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism.

ABSTRACT: Carbohydrate-responsive element binding protein (ChREBP) and Max-like protein X (MLX) form a heterodimeric transcription factor complex 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 casein kinase 2 (CK2) and glycogen synthase kinase 3 (GSK3) as MLX kinases. High intracel

SUBMITTER: Cadena Del Castillo CE 

PROVIDER: S-EPMC11900861 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature