Abstract
p53 tetramer formation is essential for DNA binding, post-translational modification, and protein–protein interaction. To clarify the threshold for dysfunction of p53 in terms of the destabilization of p53’s tetrameric structure, this study focused on the effects of tumor-associated mutations in the tetramerization domain on tetrameric structure and function. Based on a structure–function analysis of mutant p53, we also demonstrated functional regulation of p53 via the control of tetramer formation. Furthermore, we demonstrated that tumor-associated mutations in the tetramerization domain destabilized the tetrameric structure and significantly decreased the tetramer fraction in the nucleus at endogenous p53 levels. Indeed, the threshold for loss of tumor suppressor activity of p53 in terms of disruption of the tetrameric structure is suggested to be extremely low. In addition, relatively small changes in tetramer formation, induced by the stabilization or inhibition of homo-tetramerization, could control p53 function.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2012 Springer Japan
About this chapter
Cite this chapter
Kamada, R. (2012). Conclusion. In: Tetramer Stability and Functional Regulation of Tumor Suppressor Protein p53. Springer Theses. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54135-6_5
Download citation
DOI: https://doi.org/10.1007/978-4-431-54135-6_5
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-54134-9
Online ISBN: 978-4-431-54135-6
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)