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MLX磷酸化可稳定串联E-盒上的ChREBP-MLX异源四聚体，以调控碳水化合物和脂质代谢。

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

作者信息

Cadena Del Castillo Carla E, Deniz Onur, van Geest Femke, Rosseels Lore, Stockmans Ingrid, Robciuc Marius, Carpentier Sebastien, Wölnerhanssen Bettina K, Meyer-Gerspach Anne Christin, Peterli Ralph, Hietakangas Ville, Shimobayashi Mitsugu

机构信息

Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.

出版信息

bioRxiv. 2024 Sep 5:2024.09.04.611172. doi: 10.1101/2024.09.04.611172.

DOI:10.1101/2024.09.04.611172
PMID:39282306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11398402/
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 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.

摘要

异源二聚体ChREBP-MLX转录因子复合物是将细胞内糖水平与碳水化合物和脂质代谢相联系的关键介质。为促进靶基因的表达，两个ChREBP-MLX异源二聚体形成一个异源四聚体，以结合具有两个相邻E盒的串联元件，即碳水化合物反应元件（ChoRE）。ChREBP-MLX异源四聚体化是如何实现和调控的，目前仍知之甚少。在这里，我们表明，在一个进化保守基序上的MLX磷酸化对于在ChoRE上形成异源四聚体以及ChREBP-MLX复合物的转录活性是必要的。我们确定CK2和GSK3为协同磷酸化MLX的MLX激酶。细胞内高葡萄糖-6-磷酸积累会抑制MLX磷酸化以及在ChoRE上的异源四聚体形成，损害ChREBP-MLX活性。在生理上，MLX磷酸化对于维持糖耐量和脂质稳态是必要的。我们的研究结果表明，MLX磷酸化是ChREBP-MLX异源四聚体形成以调节碳水化合物和脂质代谢的关键机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/394383b4eb3f/nihpp-2024.09.04.611172v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/75049ed09ba3/nihpp-2024.09.04.611172v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/b72e1a2da533/nihpp-2024.09.04.611172v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/f6242ce8ba5b/nihpp-2024.09.04.611172v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/09dc1e7fa4fd/nihpp-2024.09.04.611172v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/417f7c71a308/nihpp-2024.09.04.611172v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/394383b4eb3f/nihpp-2024.09.04.611172v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/75049ed09ba3/nihpp-2024.09.04.611172v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/b72e1a2da533/nihpp-2024.09.04.611172v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/f6242ce8ba5b/nihpp-2024.09.04.611172v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/09dc1e7fa4fd/nihpp-2024.09.04.611172v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/417f7c71a308/nihpp-2024.09.04.611172v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/11398402/394383b4eb3f/nihpp-2024.09.04.611172v2-f0006.jpg

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Nature. 2024 Jun;630(8016):493-500. doi: 10.1038/s41586-024-07487-w. Epub 2024 May 8.
2
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Oncogene. 2023 Oct;42(43):3182-3193. doi: 10.1038/s41388-023-02831-2. Epub 2023 Sep 9.
3
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Elife. 2023 Mar 15;12:e85103. doi: 10.7554/eLife.85103.
4
Search and sequence analysis tools services from EMBL-EBI in 2022.2022 年 EMBL-EBI 的搜索和序列分析工具服务。
Nucleic Acids Res. 2022 Jul 5;50(W1):W276-W279. doi: 10.1093/nar/gkac240.
5
Coordinated Cross-Talk Between the Myc and Mlx Networks in Liver Regeneration and Neoplasia.Myc 和 Mlx 网络在肝再生和肿瘤发生中的协调对话。
Cell Mol Gastroenterol Hepatol. 2022;13(6):1785-1804. doi: 10.1016/j.jcmgh.2022.02.018. Epub 2022 Mar 5.
6
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7
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9
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