Tetramer stability and functional regulation of tumor suppressor protein p53
This thesis presents the first report of the comprehensive and quantitative analysis of the effects of tumor-derived mutations on the tetrameric structure of tumor suppressor protein p53, which plays a central role in maintaining genomic integrity. Inactivation of p53 via mutation of its gene is a k...
Enregistré dans:
| Auteur principal: | |
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| Format: | Livre numérique |
| Langue: | Anglais |
| Publié: |
Tokyo :
Springer Japan
[20..].
Cham : Springer Nature |
| Édition: | 1st ed. 2012. |
| Collection: | Springer Theses, Recognizing Outstanding Ph.D. Research
|
| Accès en ligne: | Accès sur la plateforme de l'éditeur Accès sur la plateforme Istex Accès Université d'Orléans Accès INSA CVL |
| Note: |
Archives Springer e-books (Licence nationale) Archives Springer e-books (Licence nationale) |
| Autres localisations: | Voir dans le Sudoc |
| Edition sous un autre format: | • Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53, Texte imprimé, 9784431541349 • Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53, Texte imprimé, 9784431541363 • Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53, Texte imprimé, 9784431547259 • Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53, Texte imprimé, 9784431541349 |
| Résumé: | This thesis presents the first report of the comprehensive and quantitative analysis of the effects of tumor-derived mutations on the tetrameric structure of tumor suppressor protein p53, which plays a central role in maintaining genomic integrity. Inactivation of p53 via mutation of its gene is a key step in tumorigenesis. Biophysical analyses revealed that the stability of the mutant peptides varied widely. Formation of a tetrameric structure is to be critical for protein protein interactions, DNA binding, and the post-translational modification of p53. A small destabilization of the tetrameric structure therefore could result in dysfunction of tumor suppressor activity. This work suggests that the threshold for loss of tumor suppressor activity, in terms of the disruption of p53 s tetrameric structure, could be extremely low. Furthermore, functional control of p53 via tetramer formation was demonstrated, based on the structure function analysis of mutant p53. The results disclosed that relatively small changes in tetramer formation, induced by the stabilization or inhibition of homo-tetramerization, could control p53 function |
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| Description: | Archives Springer e-books (Licence nationale) Archives Springer e-books (Licence nationale) |
| ISBN: | 9784431541356 |
| ISSN: | 2190-5061 |
| Accès: | Accès en ligne pour les établissements français bénéficiaires des licences nationales Accès soumis à abonnement pour tout autre établissement Conditions particulières de réutilisation pour les bénéficiaires des licences nationales. https://www.licencesnationales.fr/springer-nature-ebooks-contrat-licence-ln-2017 |