title: The N-end rule pathway.
abstract: The N-end rule pathway is a proteolytic system in which N-terminal residues of short-lived proteins are recognized by recognition components (N-recognins) as essential components of degrons, called N-degrons. Known N-recognins in eukaryotes mediate protein ubiquitylation and selective proteolysis by the 26S proteasome. Substrates of N-recognins can be generated when normally embedded destabilizing residues are exposed at the N terminus by proteolytic cleavage. N-degrons can also be generated through modifications of posttranslationally exposed pro-N-degrons of otherwise stable proteins; such modifications include oxidation, arginylation, leucylation, phenylalanylation, and acetylation. Although there are variations in components, degrons, and hierarchical structures, the proteolytic systems based on generation and recognition of N-degrons have been observed in all eukaryotes and prokaryotes examined thus far. The N-end rule pathway regulates homeostasis of various physiological processes, in part, through interaction with small molecules. Here, we review the biochemical mechanisms, structures, physiological functions, and small-molecule-mediated regulation of the N-end rule pathway.
authors.affiliation: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tasaki
authors.forename: Shashikanth M
authors.initials: SM
authors.lastname: Sriram
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Yong Tae
authors.initials: YT
authors.lastname: Kwon
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D009363:Neoplasm Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D025801:Ubiquitin; C021081:recognins