title: Pac-Man for biotechnology: co-opting degrons for targeted protein degradation to control and alter cell function.
abstract: Protein degradation in normal living cells is precisely regulated to match the cells' physiological requirements. The selectivity of protein degradation is determined by an elaborate degron-tagging system. Degron refers to an amino acid sequence that encodes a protein degradation signal, which is oftentimes a poly-ubiquitin chain that can be transferred to other proteins. Current understanding of ubiquitination dependent and independent protein degradation processes has expanded the application of degrons for targeted protein degradation and novel cell engineering strategies. Recent findings suggest that small molecules inducing protein association can be exploited to create degrons that target proteins for degradation. Here, recent applications of degron-based targeted protein degradation in eukaryotic organisms are reviewed. The degron mediated protein degradation represents a rapidly tunable methodology to control protein abundance, which has broad application in therapeutics and cellular function control and monitoring.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Geng
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Julian N
authors.initials: JN
authors.lastname: Rosenberg
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Betenbaugh
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Synaptic Research LLC, 1448 S. Rolling Rd, Halethorpe, Baltimore, MD 21227, USA. Electronic address: george@synapticresearch.com.
authors.forename: George A
authors.initials: GA
authors.lastname: Oyler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001709:Biotechnology; D002468:Cell Physiological Phenomena; D006801:Humans; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: D011506:Proteins