Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53 (Springer Theses) - Softcover

Kamada, Rui

Softcover

ISBN 10: 4431547258 ISBN 13: 9784431547259

Publisher: Springer, 2014

Synopsis

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.

About this title

About the Author

Dr. Rui Kamada
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University

From the Back Cover

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.

Edition details

• Publisher: Springer
• Publication date: 2014
• Language: English
• ISBN 10: 4431547258
• ISBN 13: 9784431547259
• Binding: Paperback
• Number of pages: 88