Molecular mechanisms of protein degradation
One of the main goals pursued in our group is to understand how different proteins are turned over. In particular, we have a strong interest in unraveling how cellular decisions are made to determine if proteins are degraded, and the mechanisms to coordinate this in a dynamically changing cellular environment
* Benke, S., Agerer, B., Haas, I. Stöger, M. et al. (2017). Human tripartite motif protein 52 is required for cell context-dependent proliferation. In revision.
* Rajsbaum, R., Versteeg, G.A. Schmid, S. Maestre, AM., et al. (2014). Unanchored K48-Linked Polyubiquitin Synthesized by the E3-Ubiquitin Ligase TRIM6 Stimulates the Interferon-IKK? Kinase-Mediated Antiviral Response. Immunity; 40(6):880-95.
Projects within VBC Ubiquitin Club
Failure of proper protein degradation can result in the production of non-physiological amounts of protein, which is often associated with disease. In this context, dysregulation of protein degradation often disrupts proper cell signaling and consequently results in uncontrolled immune activation, and cell proliferation. Thereby, it contributes to the development of different types of inflammatory disorders and cancers. Therefore, understanding how protein degradation is controlled at a molecular level is crucial for unraveling how many pro-inflammatory mediators, tumor suppressors, and oncoproteins are dysregulated in disease.
Currently we are using CRISPR-based genome-wide screening approaches to identify regulators of stability of several conceptually different types of inherently or inducibly unstable proteins. These efforts are combined with cell biological and biochemical techniques to understand how these identified factors regulate protein stability at a molecular level, and what their importance is for maintaining homeostasis.