General Introduction -- 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 -- Conclusion
Summary
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 tetra
Notes
"Doctoral thesis accepted by Hokkaido University, Japan" t.p