USP24 stabilizes bromodomain containing proteins to promote lung cancer malignancy
| Autor: | Ming Jer Young, Wen Yih Jeng, Shao An Wang, Chia Yu Liu, Jan Jong Hung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lung Neoplasms
Transcription Genetic Chromatin remodelling Deubiquitylating enzymes Chromatin remodeling Article Deubiquitinating enzyme Ubiquitin Cell Movement Cell Line Tumor Gene expression medicine Humans Lung cancer Cell Proliferation A549 cell Multidisciplinary biology Chemistry Protein Stability medicine.disease Bromodomain Cell culture A549 Cells biology.protein Cancer research Disease Progression Molecular modelling Non-small-cell lung cancer Ubiquitin Thiolesterase |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Bromodomain (BRD)-containing proteins are important for chromatin remodeling to regulate gene expression. In this study, we found that the deubiquitinase USP24 interacted with BRD through its C-terminus increased the levels of most BRD-containing proteins through increasing their protein stability by the removal of ubiquitin from Lys391/Lys400 of the BRD. In addition, we found that USP24 and BRG1 could regulate each other through regulating the protein stability and the transcriptional activity, respectively, of the other, suggesting that the levels of USP24 and BRG1 are regulated to form a positive feedback loop in cancer progression. Loss of the interaction motif of USP24 eliminated the ability of USP24 to stabilize BRD-containing proteins and abolished the effect of USP24 on cancer progression, including its inhibition of cancer cell proliferation and promotion of cancer cell migration, suggesting that the interaction between USP24 and the BRD is important for USP24-mediated effects on cancer progression. The targeting of BRD-containing proteins has been developed as a strategy for cancer therapy. Based on our study, targeting USP24 to inhibit the levels of BRD-containing proteins may inhibit cancer progression. |
| Databáze: | OpenAIRE |
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