Novel Breast Cancer Therapeutics Based on Bacterial Cupredoxin
Abstract
The tumor suppressor p53 is a major player in cell growth, genomic stability and cell death. Recent in vivo work suggested that bacterial Pseudomonas aeruginosa azurin can enter cancer cells and interact with p53 promoting cell death. Despite being a novel concept to target cancer, there are no thermodynamic details known for the proposed azurin-p53 complex. This project aims to fill this gap by employing biophysical methods in conjunction with purified proteins in vitro to address four aims. We will reveal (1.) which p53 domain interacts with azurin and probe affinity and stoichiometry, (2.) the molecular mechanism by which azurin increases cellular levels of p53, (3.) the region on azurin that interacts with p53 and (4.) use the acquired information to propose smaller molecules that retain properties of azurin. During the year, several discoveries have been made: most importantly, azurin is found to bind to the unstructured N-terminal domain of p53 and a small 13-residue peptide is able to reproduce part of the azurin interaction. Better biophysical understanding of azurin's interaction with p53 in vitro may be the gateway to innovative treatments of cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA484653
Entities
People
- Pernilla Wittung-Stafshede
Organizations
- Rice University