Research Projects

Ubiquitination is a reversible protein modification that plays a crucial role in cellular processes. Ubiquitin, a 76-aminoacid polypeptide, is attached covalently to substrates in an ATP-dependent manner through a sequential 3-step process mediated by three sets of enzymes: E1 activating enzyme, E2 conjugating enzyme, and E3 ligases. E3 ligases determine substrate specificity and diversity of ubiquitin chain linkages. They are classified into RING E3-ligases and HECT E3-ligases, and a third class, the RING-in between-RING (RBR) family, has been identified. The proposed work aims to understand the possible roles and regulation of RBR E3 ligases by dissecting protein complexes associated with different RBR E3-ligases. There are 14 RBR E3 ligases in humans, and using biochemical purification and proteomic approaches, the protein complexes associated with all RBR E3-ligases will be identified. The importance of these proteins will be characterized through biochemical and cellular assays. This proposal aims to uncover regulators and substrates linked with different RBR E3-ligases, potentially providing new possibilities for understanding ubiquitin-controlled cellular signaling.