دورية أكاديمية
MTA1 Coregulator Regulates p53 Stability and Function
| العنوان: | MTA1 Coregulator Regulates p53 Stability and Function |
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| المؤلفون: | Li, Da Qiang, Reddy, Sirigiri Divijendra Natha, Pakala, Suresh B., Wu, Xifeng, Zhang, Yanping, Rayala, Suresh K., Kumar, Rakesh |
| المصدر: | The Journal of Biological Chemistry, 284(50) |
| سنة النشر: | 2009 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Mice, Knockout, DNA Repair, Fibroblasts, DNA Damage, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, Transcription Factors, Humans, Animals, Recombinant Fusion Proteins, Nuclear Proteins, Cell Line, Tumor, Cells, Cultured |
| الوصف: | Although metastasis-associated protein 1 (MTA1) has recently been shown as a DNA damage responsive protein, the underlying mechanism for its role in DNA double-strand break (DSB) repair remains unknown. Here, we show that MTA1 controls p53 stability through inhibiting its ubiquitination by E3 ubiquitin ligases mouse double minute 2 (Mdm2) and constitutive photomorphogenic protein 1 (COP1). The underlying mechanisms involve the ability of MTA1 to compete with COP1 to bind to p53 and/or to destabilize COP1 and Mdm2. Consequently, MTA1 regulates the p53-dependent transcription of p53R2, a direct p53 target gene for supplying nucleotides to repair damaged DNA. Depletion of MTA1 impairs p53-dependent p53R2 transcription and compromises DNA repair. Interestingly, these events could be reversed by MTA1 reintroduction, indicating that MTA1 interjects into the p53-dependent DNA repair. Given the fact that MTA1 is widely up-regulated in human cancers, these findings in conjunction with our earlier finding of a crucial role of MTA1 in DSB repair suggest an inherent role of the MTA1-p53-p53R2 pathway in DNA damage response in cancer cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/8171-3735Test; https://cdr.lib.unc.edu/downloads/xs55mm53k?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/xs55mm53kTest |
| DOI: | 10.17615/8171-3735 |
| الإتاحة: | https://doi.org/10.17615/8171-3735Test https://cdr.lib.unc.edu/downloads/xs55mm53k?file=thumbnailTest https://cdr.lib.unc.edu/downloads/xs55mm53kTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.A4B2E97 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/8171-3735 |
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