Transcriptional repression of Sin3B by Bmi-1 prevents cellular senescence and is relieved by oncogene activation
| Autor: | Anthony J. Bainor, David J. Cantor, Gregory David, Teresa DiMauro |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Senescence
Cancer Research Transcription Genetic Polycomb: Bmi1 Regulator Repressor Biology Article 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Proto-Oncogene Proteins Genetics Animals Molecular Biology Psychological repression Cells Cultured Cellular Senescence 030304 developmental biology Cell Proliferation Regulation of gene expression Polycomb Repressive Complex 1 0303 health sciences Oncogenes Phenotype Chromatin Up-Regulation Gene Expression Regulation Neoplastic Repressor Proteins 030220 oncology & carcinogenesis Cancer research Cell aging Transcription Sin3 |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | The Polycomb group protein Bmi-1 is an essential regulator of cellular senescence and is believed to function largely through the direct repression of the Ink4a/Arf locus. However, concurrent deletion of Ink4a/Arf does not fully rescue the defects detected in Bmi-1(-/-) mice, indicating that additional Bmi-1 targets remain to be identified. The expression of the chromatin-associated Sin3B protein is stimulated by oncogenic stress, and is required for oncogene-induced senescence. Here we demonstrate that oncogenic stress leads to the dissociation of Bmi-1 from the Sin3B locus, resulting in increased Sin3B expression and subsequent entry into cellular senescence. Furthermore, Sin3B is required for the senescent phenotype and elevated levels of reactive oxygen species elicited upon Bmi-1 depletion. Altogether, these results identify Sin3B as a novel direct target of Bmi-1, and establish Bmi-1-driven repression of Sin3B as an essential regulator of cellular senescence. |
| Databáze: | OpenAIRE |
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