Image modified from Freepik.

In proteomics, targeted protein degradation (TPD) has emerged as a powerful approach to directly edit the proteome, complementing genetic techniques like CRISPR and siRNA. A recent research paper by Taylor et al. explores the use of human E2 ubiquitin-conjugating enzymes, such as UBE2D1 and UBE2B, as alternative degradation domains for bioPROTACs – fusion proteins that recruit target proteins to the ubiquitin-proteasome system (UPS) for degradation.

The researchers demonstrate that E2 bioPROTACs can effectively induce the degradation of disease-associated proteins, including SHP2 and KRAS, within cancer cell lines.

Overall, this research showcases the potential of E2 enzymes as an alternative platform for targeted protein degradation, with possible applications in fundamental research, cell engineering, and disease management.

Peptides were separated on an IonOpticks Aurora Ultimate 25×75 C18 UHPLC column.

Publication
Communications Biology

Authors

Jonathan D. Taylor, Nathalie Barrett, Sergio Martinez Cuesta, Katelyn Cassidy, Fiona Pachl, James Dodgson, Radhika Patel, Tuula M. Eriksson, Aidan Riley, Matthew Burrell, Christin Bauer, D. Gareth Rees, Raffaello Cimbro, Andrew X. Zhang, Ralph R. Minter, James Hunt, & Sandrine Legg

Title

Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes