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Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53

Rui Kamada (Autor)

Buch | Hardcover

74 Seiten

2012
Springer Verlag, Japan
978-4-431-54134-9 (ISBN)

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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.

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

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.

Erscheint lt. Verlag	21.7.2012
Reihe/Serie	Springer Theses
Zusatzinfo	XIV, 74 p.
Verlagsort	Tokyo
Sprache	englisch
Maße	155 x 235 mm
Themenwelt	Medizin / Pharmazie ► Pharmazie
	Naturwissenschaften ► Biologie ► Biochemie
	Naturwissenschaften ► Chemie ► Organische Chemie
Schlagworte	Mutation
ISBN-10	4-431-54134-9 / 4431541349
ISBN-13	978-4-431-54134-9 / 9784431541349
Zustand	Neuware