The nucleolus directly regulates p53 export and degradation
| العنوان: | The nucleolus directly regulates p53 export and degradation |
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| المؤلفون: | Carlos P. Rubbi, Nikolina Vlatkovic, Mark T. Boyd |
| المصدر: | The Journal of Cell Biology |
| بيانات النشر: | The Rockefeller University Press, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cyclin-Dependent Kinase Inhibitor p21, Ribosomal Proteins, Cytoplasm, Proteasome Endopeptidase Complex, Nucleolus, Leupeptins, Recombinant Fusion Proteins, Green Fluorescent Proteins, Active Transport, Cell Nucleus, Models, Biological, Article, Cell Fusion, Mice, Proto-Oncogene Proteins c-mdm2, Ubiquitin, Cell Line, Tumor, medicine, Nucleolus Organizer Region, Animals, Humans, Cycloheximide, Cellular localization, Research Articles, Cell Nucleus, Photobleaching, biology, Demecolcine, Ubiquitination, Cell Biology, 3T3 Cells, Cell biology, Cell nucleus, medicine.anatomical_structure, biology.protein, Fatty Acids, Unsaturated, Nucleolus organizer region, Cell fractionation, Intranuclear Space, Tumor Suppressor Protein p53, Cell Nucleolus, DNA Damage, Subcellular Fractions |
| الوصف: | Nucleoli directly regulate p53 export and degradation rather than simply sequestering p53 regulatory factors. The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety of cellular stresses. This link may be caused by steps in p53 regulation occurring in nucleoli, as suggested by some biochemical evidence. Alternatively, nucleolar disruption also causes redistribution of nucleolar proteins, potentially altering their interactions with p53 and/or MDM2. This raises the fundamental question of whether the nucleolus controls p53 directly, i.e., as a site where p53 regulatory processes occur, or indirectly, i.e., by determining the cellular localization of p53/MDM2-interacting factors. In this work, transport experiments based on heterokaryons, photobleaching, and micronucleation demonstrate that p53 regulatory events are directly regulated by nucleoli and are dependent on intact nucleolar structure and function. Subcellular fractionation and nucleolar isolation revealed a distribution of ubiquitylated p53 that supports these findings. In addition, our results indicate that p53 is exported by two pathways: one stress sensitive and one stress insensitive, the latter being regulated by activities present in the nucleolus. |
| اللغة: | English |
| تدمد: | 1540-8140 0021-9525 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::127e7f7be0774859f24a57c3f367540bTest http://europepmc.org/articles/PMC3171122Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....127e7f7be0774859f24a57c3f367540b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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