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Ell3 functions as a critical decision maker at the crossroad between stem cell senescence and apoptosis

BACKGROUND: Ell3 is a RNA polymerase II elongation factor that has various cell type-dependent functions, such as regulating the differentiation efficiency of embryonic stem cells and sensitizing cancer cells to anticancer drugs. However, there has been little research on the role of Ell3 on the reg...

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Detalles Bibliográficos
Autores principales: Lee, Jae-Yong, Lee, Soo-Hong, Kim, Kwang-Soo, Park, Keun-Hong, Park, Kyung-Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335702/
https://www.ncbi.nlm.nih.gov/pubmed/30654843
http://dx.doi.org/10.1186/s13287-019-1137-9
Descripción
Sumario:BACKGROUND: Ell3 is a RNA polymerase II elongation factor that has various cell type-dependent functions, such as regulating the differentiation efficiency of embryonic stem cells and sensitizing cancer cells to anticancer drugs. However, there has been little research on the role of Ell3 on the regulation of senescence and apoptosis of stem cells. METHODS: We analyzed the senescence of Ell3-suppressed stem cells by mitochondrial activity, β-gal (+) cells, and lineage differentiation efficiency. The apoptosis of Ell3-overexpressing stem cells was analyzed by Annexin V staining, Immunoblot, and Live&dead assay. In addition, chromatin immunoprecipitation and luciferase assays were used to demonstrate p53 functions as a direct transcriptional activator of Ell3. RESULTS: Suppression of Ell3 expression induced senescence in stem cells by increasing Bcl-2 expression. Unlike the effect of Ell3 suppression, the ectopic expression of Ell3 induces apoptosis of stem cells and induces apoptosis of adjacent cells. In addition, p53 functions as a direct transcriptional activator of Ell3 during the stem cell apoptosis. CONCLUSIONS: We suggest that the function of Ell3 is associated with the p53-Bcl2 axis in both senescent and apoptotic ADSCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1137-9) contains supplementary material, which is available to authorized users.