Title: Biophysical Characterization of the p53 DNA Binding Domain Hotspot Mutations
Abstract:Author(s): Lefever, Kevin Jacob | Abstract: p53 is a tumor cell suppressor protein that is activated upon cellular stress to induce DNA repair, senescence, or apoptosis. Its importance can be seen in ...Author(s): Lefever, Kevin Jacob | Abstract: p53 is a tumor cell suppressor protein that is activated upon cellular stress to induce DNA repair, senescence, or apoptosis. Its importance can be seen in that 50% of human cancers have a mutation in the TP53 gene, and in the greatly increased probability for cancer in Li-Fraumeni syndrome patients, in which germline mutations in the TP53 gene increase the probability of homozygous The vast majority of p53 mutations found in cancer are located in a few key residues of the DNA-binding domain (DBD) of the protein, referred to as mutations. The goal of this thesis is to elucidate the structural and biophysical properties of four p53 hotspot mutants in order to better understand their inactivation mechanism. I have shown these common mutants have a severely reduced ability to bind DNA, while retaining the majority of the three dimensional structure. Additionally, I show that these mutants as well as the wild-type p53 DBD form amyloid fibers at high concentrationsRead More
Publication Year: 2014
Publication Date: 2014-01-01
Language: en
Type: article
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot