W2476 represses TXNIP transcription via dephosphorylation of FOXO1 at Ser319
| Autor: | Li Zhong, Yongbing Cao, Qiaofeng Liu, Dehua Yang, Shikai Zhang, Ming-Wei Wang, Qing Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Transcription Genetic Response element Cell Cycle Proteins Nerve Tissue Proteins FOXO1 01 natural sciences Biochemistry Histone H4 Insulin-Secreting Cells Drug Discovery Animals Phosphorylation Rats Wistar Promoter Regions Genetic Carbohydrate-responsive element-binding protein Transcription factor Cells Cultured Pharmacology Histone Acetyltransferase p300 Basic Helix-Loop-Helix Leucine Zipper Transcription Factors 010405 organic chemistry Chemistry Adenine Organic Chemistry Rats 0104 chemical sciences Cell biology 010404 medicinal & biomolecular chemistry Glucose Molecular Medicine Proto-Oncogene Proteins c-akt Chromatin immunoprecipitation TXNIP Protein Binding |
| Zdroj: | Chemical Biology & Drug Design. 97:1089-1099 |
| ISSN: | 1747-0285 1747-0277 |
| DOI: | 10.1111/cbdd.13828 |
| Popis: | Thioredoxin-interacting protein (TXNIP) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve β-cell dysfunction and exert therapeutic effects in diabetic mice via repression of TXNIP signaling pathway. The impact of W2476 on TXNIP transcription was thus investigated using the chromatin immunoprecipitation method. It was found that W2476 promotes competitive binding of forkhead box O1 transcription factor (FOXO1) to the carbohydrate response element (ChoRE) sequence associated with ChoRE-binding protein (ChREBP)/Mlx interacting protein-like(Mlx) complexes. This interaction hinders the attachment of histone acetyltransferase p300 and reduces histone H4 acetylation on the TXNIP promoter, leading to decreasing TXNIP transcription. |
| Databáze: | OpenAIRE |
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