Buch, Englisch, 74 Seiten, Format (B × H): 160 mm x 241 mm, Gewicht: 307 g
Reihe: Springer Theses
Buch, Englisch, 74 Seiten, Format (B × H): 160 mm x 241 mm, Gewicht: 307 g
Reihe: Springer Theses
ISBN: 978-4-431-54134-9
Verlag: Springer Japan
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.
Zielgruppe
Research
Autoren/Hrsg.
Fachgebiete
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Klinische und Innere Medizin Onkologie, Krebsforschung
- Naturwissenschaften Biowissenschaften Proteinforschung
- Naturwissenschaften Chemie Organische Chemie Biochemie
- Naturwissenschaften Biowissenschaften Biochemie (nichtmedizinisch)
- Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizin, Gesundheitswesen Biomedizin, Medizinische Forschung, Klinische Studien
Weitere Infos & Material
Quantitative analysis for p53 tetramerization domain mutants reveals a low threshold for tumor suppressor inactivation.- Stabilization of mutant tetrameric structures by calixarene derivatives.- Inhibition of the transcriptional activity of p53 through hetero-oligomerization.
