Ubiquitination is one of the most widespread post-translational modifications (PTMs) that regulate several signaling pathways within eukaryotic cells. Covalent attachment of ubiquitin (Ub) to various protein substrates is fundamental to almost every important cellular process such as proteasomal degradation, mitophagy, DNA damage response, protein quality control, and more.  Ubiquitination is usually not a singular modification, but rather generally involves the subsequent attachment of the C-terminus of one Ub molecule to a lysine of another Ub moiety, giving rise to polyubiquitin chains with distinct Ub linkages, each playing different roles in cellular homeostasis. Ub-Ub linkages mediated by Ub residue Lys48 (K48-linked polyUb chains) usually designate the protein for proteasomal degradation, while polyubiquitin chains formed on proteins via Lys63 (K63-linked chains) mediate endo-lysosomal trafficking associated with cell-surface receptor signaling and membrane protein turnover. Such a tightly regulated protein quality control mechanism is essential for maintaining cellular protein homeostasis or proteostasis. The specificity of both ubiquitination substrate and polyubiquitin linkage type relies on the activity of E3 ligases. This presentation will include our attempt to develop peptide-based E3 ligase activity assays which can quantitatively be used to characterize substrate recruitment. In addition, this activity assay will also allow the identification of novel competitive inhibitors of E3 ligases.

Development of an E3 ligase activity assay for novel ligand identification

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.