Degradomics – Proteomic Identification of protease substrates in vitro and in vivo
Stefan Lichtenthaler, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Proteolysis is an irreversible post-translational modification mediated by nearly 600 different proteases in man.
Proteases control the function or mediate the degradation of virtually all proteins in the cell, but the biological functions of many proteases are unknown, because no or only few physiological substrates have been identified. Degradomics is the application of genomic and proteomic approaches to identify proteases and their substrates.
Proteomic protease substrate identification from cells is frequently done by methods such as SPECS, TAILS and COFRADIC and will be demonstrated in detail for the proteases BACE1 and ADAM10, which have key roles in Alzheimer’s disease, inflammation and cancer. Additionally, the talk will show how protease substrates can be identified from in vivo material (tissues and body fluids) of protease knock-out mice.
The substrate identification is not only essential for a better understanding of the physiological function of a protease, but also for evaluating its therapeutic potential and for the prediction of potential side-effects resulting from therapeutic protease inhibition.
