Skip to main content
Utah's Foremost Platform for Undergraduate Research Presentation
2013 Abstracts

Rationally Modified Tumor Suppressor Protein p53: A Possible New Cancer Treatment

Thomas Wallace, University of Utah

Pharmaceutics and Pharmaceutical Chemistry

The tumor suppressor p53 is mutated in more than 50% of all cancers, while the majority of remaining cancers contain mislocalized p53(1). p53 is part of a network of cellular pathways that regulate growth, cell cycle arrest, and clearly delineated apoptotic pathways(2). Restoring the function of p53 can be seen as an ultimate cancer treatment. Restoring p53 would activate an already existing cell pathway that prevents cells from becoming cancerous and cause cancer cells to go through apoptosis. Playing a role in tumor suppression has made p53 an attractive target for gene therapy. However, despite the potential of p53 as a powerful treatment, it is limited by the dominant-negative effect of dysfunctional mutant p53. This effect imposes one of the greatest limits on the effectiveness of a p53 based treatment. This project is focused on bypassing the dominant-negative effect of dysfunctional p53 over exogenous functional p53. The attempted solution was substitution of the p53 binding domain with a different but structurally analogous coiled-coil, based on a modified Breakpoint cluster region (Bcr) protein. By doing this, the dominant-negative effect of mutant p53 may be bypassed. The purpose of this project has been to synthesis and test rationally modified forms of p53 with modified Bcr coil that are introduced into cells via a plasmid to restore cellular p53 activity. In vivo cell tests have already shown the effectiveness of these constructs at causing higher rates of cell death in cancer cells and constructs are currently being refined to carry forward to xenograft model animal trails. The ultimate goal is to develop a treatment for human cancer patients where modified p53 will selectively cause apoptosis in cancer cells.