Proteolysis-mediating Protein Complexes
Research report (imported) 2005 - Max Planck Institute of Biochemistry
Our research focuses on the regulation of substrate specificity in the ubiquitin proteasome system, specifically on two modular protein complexes: the CBCVHL ubiquitin ligase with its substrate binding subunit, the von-Hippel-Lindau tumor suppressor protein, and the chaperone-like Cdc48 AAA ATPase with cofactors of the UBX protein family. UBX proteins bind to Cdc48 and thereby regulate the specificity of Cdc48 activity in various cellular processes. UBX proteins with a ubiquitin binding UBA domain recruit ubiquitylated substrates which are targeted via Cdc48 for proteasomal degradation. One such UBA/UBX protein, called Ubx2, plays a central role in endoplasmic reticulum (ER) associated protein degradation (ERAD). Biochemical studies of tumor associated mutants of the von-Hippel-Lindau tumor suppressor protein provide new insights in the complex genotype/phenotype relationship of the von-Hippel-Lindau disease. For instance, the extent of functional defects on the molecular level correlates with the patients´ risk of developing renal cell carcinomas.