title: Targeted protein degradation.
abstract: The ubiquitin-proteasome pathway plays a major role in cellular protein destruction and regulates fundamental cellular processes such as the cell cycle, cell signaling, and development. By altering the substrate recognition of ubiquitin-protein ligases, their robust proteolytic activity can be re-directed to recruit and accelerate the degradation of other cellular targets. Two approaches have been applied for targeted proteolysis: one entails designing a chimeric substrate receptor for recruitment of the target protein, the other involves the construction of peptide-small-molecule hybrids that bridge the interaction between the intended target and the substrate receptor of the known ubiquitin-protein ligases. The engineered ubiquitin-proteolytic apparatus operates at the post-translational level, and thus provides a new tool of reverse genetics to dissect complicated protein functions at a higher resolution than knockout or knockdown approaches functioning at the level of DNA or RNA. It also sheds light on novel therapeutic strategies for the amelioration of human disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. pez2001@med.cornell.edu
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhou
mesh_terms: D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D044783:F-Box Proteins; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex