The nuclear translocation of transketolase inhibits the farnesoid receptor expression by promoting the binding of HDAC3 to FXR promoter in hepatocellular carcinoma cell lines
| Autor: | Pan Tong, Sen Meng, Xiaoge Gao, Pingfu Hou, Dafei Chai, Minle Li, Hao-yu Quan, Xuping Zhang, Jin Bai, Xuemei Tong, Ying Lu, Junnian Zheng |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Molecular biology Receptor expression Immunology Receptors Cytoplasmic and Nuclear Transketolase Histone Deacetylases Article Bile Acids and Salts Cellular and Molecular Neuroscience Cell Line Tumor Animals Humans STAT1 lcsh:QH573-671 Promoter Regions Genetic Cancer Cell Nucleus Mice Knockout Regulation of gene expression biology lcsh:Cytology Chemistry Liver Neoplasms Cell Biology HDAC3 Cancer metabolism Cell biology Gene Expression Regulation Neoplastic Mice Inbred C57BL Protein Transport STAT1 Transcription Factor Liver Cancer cell biology.protein STAT protein Ectopic expression Protein Binding |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 1, Pp 1-11 (2020) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2225-6 |
| Popis: | Transketolase (TKT), which is a metabolic enzyme in the nonoxidative phase of the pentose phosphate pathway (PPP), plays an important role in providing cancer cells with raw materials for macromolecular biosynthesis. The ectopic expression of TKT in hepatocellular carcinoma (HCC) was reported previously. However, the role of TKT in the initiation of liver cancer is still obscure. In our previous study, we found that TKT deficiency protects the liver from DNA damage by increasing levels of ribose 5-phosphate and nucleotides. What’s more interesting is that we found TKT deficiency reduced bile acids and loss of TKT promoted the farnesoid receptor (FXR) expression. We further showed that TKT translocated into the nucleus of HCC cell lines through interacting with the signal transducer and activator of transcription 1 (STAT1), and then the complex inhibited FXR expression by promoting the binding of histone deacetylase 3 (HDAC3) to FXR promoter. |
| Databáze: | OpenAIRE |
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