ETS1 targets RYBP transcription to inhibit tumor cell proliferation
| Autor: | Wen Zhao, Xiaoyi Wang, Deng Chen, Shiqiang Zhang, Xiaoli Ma, Hong Chen, Bingren Huang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Carcinogenesis Cellular differentiation Biophysics Apoptosis Biology Biochemistry Small hairpin RNA Proto-Oncogene Protein c-ets-1 03 medical and health sciences 0302 clinical medicine ETS1 Transcription (biology) Cell Line Tumor Neoplasms Transcriptional regulation Humans Molecular Biology Cell Proliferation YY1 Intracellular Signaling Peptides and Proteins Cell Biology Cell biology Gene Expression Regulation Neoplastic Repressor Proteins 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Ectopic expression Chromatin immunoprecipitation |
| Zdroj: | Biochemical and biophysical research communications. 509(3) |
| ISSN: | 1090-2104 |
| Popis: | ETS1 (E26 transformation specific-1) is the founding member of ETS transcriptional factor family. It transcriptionally modulates numerous gene expressions, and is involved in cellular differentiation, tissue remodeling, angiogenesis, drug resistance and tumorigenesis. ETS1 is usually regarded as an oncogene. However, its apoptosis-inducing activity was also frequently reported. Here, we identified RYBP (Ring1 and YY1 binding protein), a critical epigenetic regulator and apoptosis enhancer, as a novel transcriptional target of ETS1. Specifically, we found that overexpression of ETS1 up-regulates the promoter activity of RYBP in HEK293T and tumor cells from different tissue origins, indicating a universal transcriptional regulatory effect. Subsequently, both overexpression and RNA interfering experiments demonstrated that ETS1 positively modulates RYBP expression from both mRNA and protein levels. Bioinformatics analysis combined with site-directed mutagenesis suggested that there probably exist a multiple of ETS1 binding sites in RYBP promoter region, and chromatin immunoprecipitation assay validates the physical association between ETS1 protein and RYBP promoter region. Functional studies showed that ectopic expression of ETS1 significantly suppresses tumor cell proliferation. However, this inhibitory effect was partially compromised when RYBP was concomitantly knocked down by its specific short hairpin RNA. Meanwhile, we provide evidence to demonstrate that cyclin-dependent kinase inhibitor p21 is possibly involved in this regulatory loop. Taken together, our current study identified RYBP as a new transcriptional target which is utilized by ETS1 to carry out its tumor cell growth inhibitory effect. |
| Databáze: | OpenAIRE |
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