دورية أكاديمية
The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage
| العنوان: | The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage |
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| المؤلفون: | Jeong, Eutteum, Brady, Owen A, Martina, José A, Pirooznia, Mehdi, Tunc, Ilker, Puertollano, Rosa |
| المساهمون: | National Institutes of Health |
| المصدر: | eLife ; volume 7 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2018 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | The transcription factors TFE3 and TFEB cooperate to regulate autophagy induction and lysosome biogenesis in response to starvation. Here we demonstrate that DNA damage activates TFE3 and TFEB in a p53 and mTORC1 dependent manner. RNA-Seq analysis of TFEB/TFE3 double-knockout cells exposed to etoposide reveals a profound dysregulation of the DNA damage response, including upstream regulators and downstream p53 targets. TFE3 and TFEB contribute to sustain p53-dependent response by stabilizing p53 protein levels. In TFEB/TFE3 DKOs, p53 half-life is significantly decreased due to elevated Mdm2 levels. Transcriptional profiles of genes involved in lysosome membrane permeabilization and cell death pathways are dysregulated in TFEB/TFE3-depleted cells. Consequently, prolonged DNA damage results in impaired LMP and apoptosis induction. Finally, expression of multiple genes implicated in cell cycle control is altered in TFEB/TFE3 DKOs, revealing a previously unrecognized role of TFEB and TFE3 in the regulation of cell cycle checkpoints in response to stress. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.40856 |
| الإتاحة: | https://doi.org/10.7554/elife.40856Test https://cdn.elifesciences.org/articles/40856/elife-40856-v2.pdfTest https://cdn.elifesciences.org/articles/40856/elife-40856-v2.xmlTest https://elifesciences.org/articles/40856Test |
| حقوق: | http://creativecommons.org/publicdomain/zero/1.0Test/ ; http://creativecommons.org/publicdomain/zero/1.0Test/ ; http://creativecommons.org/publicdomain/zero/1.0Test/ |
| رقم الانضمام: | edsbas.AF29AFA6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.40856 |
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