Synthetic biology approaches for targeted protein degradation

• Published in: Biotechnology advances 2019-12, Vol.37 (8), p.107446-107446, Article 107446
• Main Authors: Chen, Rebecca P., Gaynor, Andrew S., Chen, Wilfred
• Format: Article
• Language: English
• Subjects: Animals; Conditional; Degradation; Degron; Dynamic control; Homeostasis; Proteins; Proteolysis; Synthetic Biology
• ISSN: 0734-9750; 1873-1899
• DOI: 10.1016/j.biotechadv.2019.107446

Protein degradation is an effective native mechanism used in modulating intracellular information, and thus it plays an essential role in maintaining cellular homeostasis. Repurposing native protein degradation in a synthetic context is gaining attention as a new strategy to manipulate cellular behavior rapidly for a wide range of applications including disease detection and therapy. This review examines the native mechanisms and machineries by which mammalian cells degrade their own proteins including the sequence of events from identifying a candidate for degradation to the protein's destruction. Next, it explores engineering efforts to degrade both exogenous and native proteins with high specificity and control by targeting proteins into the degradation cascade. A complete understanding of design rules with an ability to use cellular information as signals will allow control over the cellular behavior in a well-defined manner. •Summarizing the two main protein degradation pathways.•Summarizing conditional protein degradation and rescue.•Highlighting proximity-based approaches for synthetic protein degradation.