Degree Granting Department
Biology (Cell Biology, Microbiology, Molecular Biology)
Gary W. Daughdrill
Isothermal Titration Calorimetry, Nuclear Magnetic Resonance
The tumor suppressor protein, p53, is mutated or dysregulated in nearly all human cancers(1). The amino terminal domains are essential for transcriptional activation in stressed cells and play a vital role in cell cycle regulation, apoptosis and senescence. The transactivation (TAD) and proline rich domains in this region are dynamic and intrinsically disordered; lacking stable secondary or tertiary structure. This region contains multiple binding sites; arguably, the most significant of these is for p53's negative regulator, the E3 ligase, MDM2. An important, but less understood interaction involving the single stranded DNA binding protein, RPA70A, is hypothesized to be involved in maintaining genome integrity(2-4). Additionally, the amino terminus contains an important single nucleotide polymorphism that has demonstrated different affinity for MDM2 and is of significant biological importance in the induction of apoptosis (5). Isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy were employed to investigate how the thermodynamics and the inherent flexibility of the amino terminus of p53 play a role in complex formation with the MDM2 or RPA70 proteins. Understanding the structure, dynamics, and function of p53 is paramount in the fight against cancer.
Scholar Commons Citation
Powell, Anne Terese, "Structure and Dynamics of the p53 Transactivation Domain Binding to MDM2 and RPA70" (2012). Graduate Theses and Dissertations.