Nucleolar control of p53: a cellular Achilles’ heel and a target for cancer therapy
| العنوان: | Nucleolar control of p53: a cellular Achilles’ heel and a target for cancer therapy |
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| المؤلفون: | Mark T. Boyd, Carlos P. Rubbi, Nikolina Vlatkovic |
| المصدر: | Cellular and Molecular Life Sciences. 71:771-791 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Nucleolus, Ribosome biogenesis, Models, Biological, Cellular and Molecular Neuroscience, Proto-Oncogene Proteins c-mdm2, Stress, Physiological, Neoplasms, Molecular Biology, Loss function, Pharmacology, Regulation of gene expression, biology, Protein Stability, Cell Biology, Compartmentalization (psychology), Cell biology, Ubiquitin ligase, Gene Expression Regulation, Neoplastic, Protein Transport, Proteolysis, biology.protein, Molecular Medicine, Mdm2, Tumor Suppressor Protein p53, Ribosomes, Cell Nucleolus |
| الوصف: | Nucleoli perform a crucial cell function, ribosome biogenesis, and of critical relevance to the subject of this review, they are also extremely sensitive to cellular stresses, which can cause loss of function and/or associated structural disruption. In recent years, we have learned that cells take advantage of this stress sensitivity of nucleoli, using them as stress sensors. One major protein regulated by this role of nucleoli is the tumor suppressor p53, which is activated in response to diverse cellular injuries in order to exert its onco-protective effects. Here we discuss a model of nucleolar regulation of p53, which proposes that key steps in the promotion of p53 degradation by the ubiquitin ligase MDM2 occur in nucleoli, thus providing an explanation for the observed link between nucleolar disruption and p53 stability. We review current evidence for this compartmentalization in p53 homeostasis and highlight current limitations of the model. Interestingly, a number of current chemotherapeutic agents capable of inducing a p53 response are likely to do so by targeting nucleolar functions and these compounds may serve to inform further improved therapeutic targeting of nucleoli. |
| تدمد: | 1420-9071 1420-682X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6dd7fd57aa0e501007055c6b6659fe24Test https://doi.org/10.1007/s00018-013-1361-xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....6dd7fd57aa0e501007055c6b6659fe24 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14209071 1420682X |
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