Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
Histochem Cell Biol. 2024 Dec;162(6):487-494. doi: 10.1007/s00418-024-02307-8. Epub 2024 Jul 22.
Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to α-ketoglutarate in cells. However, research on IDH1 is more focused on the metabolite D-2-hydroxyglutarate than the cellular roles of the IDH1 protein. Metabolic enzymes can moonlight by participating in diverse cellular processes in cancer cells. This moonlighting function of the metabolic enzymes can contribute to changes in gene expression. It is unknown whether IDH1 associates with any transcription factor. We asked whether IDH1 coordinates with forkhead box protein M1 (FOXM1) in mitotic cells to regulate late genes expression. We found that depletion of IDH1 reduces canonical FOXM1-target expression in mitotic cells. Also, IDH1 binds to FOXM1 and a subset of MuvB proteins, Lin-9 and Lin-54, in mitotic cells. Based on these observations, we suggest that IDH1 coordinates with FOXM1 in mitotic cells to regulate late genes expression.
异柠檬酸脱氢酶 1(IDH1)是一种代谢酶,可在细胞中将异柠檬酸转化为α-酮戊二酸。然而,IDH1 的研究更多地集中在代谢物 D-2-羟基戊二酸上,而不是 IDH1 蛋白的细胞功能上。代谢酶可以通过参与癌细胞中的多种细胞过程来兼职。代谢酶的这种兼职功能可能导致基因表达的变化。目前尚不清楚 IDH1 是否与任何转录因子相关。我们询问 IDH1 是否与有丝分裂细胞中的叉头框蛋白 M1(FOXM1)协调以调节晚期基因表达。我们发现,IDH1 的耗竭减少了有丝分裂细胞中典型的 FOXM1 靶基因的表达。此外,IDH1 在有丝分裂细胞中与 FOXM1 和 MuvB 蛋白的一部分,Lin-9 和 Lin-54 结合。基于这些观察结果,我们认为 IDH1 在有丝分裂细胞中与 FOXM1 协调以调节晚期基因表达。