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Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53

by Rui Kamada
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Rui Kamada Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53
Rui Kamada - Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53

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Description

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.

Contributors

Author:
Rui Kamada

Further information

Illustrations Note:
6 schwarz-weiße und 39 farbige Abbildungen
remarks:

Nominated by Hokkaido University as an outstanding thesis in chemistry


First report that comprehensively and quantitatively analyzes the effects of tumor-derived mutations on tetrameric structure of tumor suppressor p53


Reports the development of a new stabilizer and inhibitor of p53, which could enhance or decrease p53 transcriptional activity via regulation of tetramer formation of p53


Media Type:
Buch
Publisher:
Springer Tokyo
Biography Artist:
Dr. Rui Kamada
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University
Language:
Englisch
Number of Pages:
71
summary:
This book 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.

Master Data

Product Type:
Hardback book
Release date:
21 July 2012
Package Dimensions:
0.234 x 0.158 x 0.012 m; 0.28 kg
GTIN:
09784431541349
DUIN:
9074B9RC577
Manufacturer Part Number:
35231363
£87.92
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