11/14 - Seminar (chem bio): Kate Caroll, Scripps Florida
Kate Caroll - speaker's website
Department of Chemistry
The Scripps Research Institute
Host: Dorothea Fiedler
Painting the Cysteine Chapel: New Tools to Probe Oxidation Biology
Reversible oxidation of cysteine residues has emerged as a central mechanism for dynamic, post-translational regulation of proteins from all major functional classes and is known to correlate with disease states. However, a significant challenge in elucidating the diverse roles of cysteine oxidation in physiology and pathology has been the difficultly in detecting these modifications in complex biological systems with chemical specificity. This presentation will briefly highlight advances in the development of chemical methods for the direct detection and labeling of cysteine post-translational modifications within their native cellular environment. Subsequently, we describe how the activity of protein kinases and phosphatases can be regulated through signaling-dependent changes in cysteine oxidation. As a case study, we will discuss new data on the oxidation of an active site cysteine in the epidermal growth factor receptor (EGFR), which stimulates the intrinsic tyrosine kinase activity of this enzyme. These data implicate redox-regulation of kinases as a potentially important driver of the cancer development process. Lastly, we will discuss how these findings may serve as the basis for developing novel therapeutics that target redox-modified proteins.