Cullin4-RING Ubiquitin Ligases (Schwefel Lab)
The Schwefel lab is interested in
- the molecular mechanisms of substrate protein recognition,
- the cellular consequences of substrate modification with ubiquitin,
- the interaction of Cullin4-RING ligases with viral proteins, and how these binding processes change the substrate specificity.
In addition, we study the interaction of Cullin4-RING ligases with viral proteins, and how these binding processes change the substrate specificity.
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Substrate recognition and specificity modulation of Cullin4-RING ubiquitin ligases ("Emmy Noether Programme", DFG)
Cullin4-RING E3 ubiquitin ligases evolved a modular architecture for the targeted modification of cellular proteins with ubiquitin, in order to mark substrates for proteasomal degradation or to induce other regulatory processes, with implications for DNA repair, DNA replication and cell cycle control.
Substrates are specifically recognised by exchangeable receptors (DCAFs, Table 1), which are connected to the Cullin4-RING sub-complex via an adapter protein (DDB1, Figure 1A). This modular architecture of Cullin4-RING ligases ensures proper placement of the substrate for ubiquitin transfer (Figure 1B).
Table: Putative DCAFs identified (+) in proteomic screens using DDB1 as bait.
|[Englische Übersetzung] DCAF||Jin et al.||He et al.||Angers et al.||Higa et al.||Human interactome|
The following issues are addressed in the Schwefel lab on a molecular level:
- How is the substrate receptor DCAF1 integrated in the E3 ligase complex, how are substrate proteins specifically recognised, and what are the consequences for the substrate and the cell?
- The interaction of DCAF1 with accessory proteins from immunodeficiency viruses will be studied, in order to understand the molecular mechanism of virus-induced DCAF1 specificity modulation and the resulting degradation of antiviral factors. This approach will not only provide insights into viral modification of the Cullin4-RING system, but also contribute to further understanding of retroviral replication.
- Potential substrates of yet uncharacterised DCAFs will be identified, to gain new insights into Cullin4 receptor specificity and hence into the biology of the Cullin4-RING system.