Determinants of protein stability in cells
The coordination of protein synthesis and degradation for the regulation of protein abundance is a fundamental aspect of cellular homeostasis determining a cell’s function and enabling it to respond to diverse stimuli. Disruption of this tight control can lead to all kinds of diseases including cancer. Although mass spectrometry based, proteomics technologies nowadays in principle allow for determination of native protein turnover, the comparative study of protein stability under different experimental conditions is challenging. Moreover, information on factors influencing cellular protein stability on a global scale is still sparse.
By development and evaluation of new workflows and proteome-wide determination of protein synthesis and degradation rates under different biological settings, we aim to identify factors influencing protein stability, thereby eventually improving our global understanding of cellular proteostasis in health and disease. In addition, multidimensional proteome and posttranslational modification profiling upon treatment with drugs affecting proteostasis should not only help to further elucidate the mode of action of the drugs, but should also expand our knowledge about protein folding and degradation pathways.