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Project Title: Engineered bacterial novel E3 ligase (NEL) targeting cancer-associated protein for degradation
Summary: The ubiquitin-proteasome pathway (UPP) is the main route of protein degradation in eukaryotic cells and the common mechanism regulated by numerous cellular pathways. Recently, manipulating the UPP to achieve targeted silencing of cellular proteins has emerged as a reliable strategy for mammalian proteome regulation. Similar with Eukaryotic E3 ligase, some bacterial effectors also have the capacity to hijack the host ubiquitin system, facilitating the transfer of ubiquitin to exposed lysine residues on substrate proteins and catalyzing the formation of ubiquitin chains upon ectopic expression within host cells, thereby inducing the degradation of substrate proteins. Thus, by compromising bacterial novel E3 ligase (NEL) and target protein ligand together, it will be possible to achieve precise localization and ubiquitination of the target protein.
In this research project, we will use ribosome display technique to conduct a screening of ligands for the cancer-associated protein and further employ engineered bacteria as a delivery system for NEL- target protein ligand chimeras, aiming to achieve directional degradation of target proteins.
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