title: cis-trans recognition and subunit-specific degradation of short-lived proteins.
abstract: The N-end rule, a code that relates the metabolic stability of a protein to the identity of its amino-terminal residue, is universal in that different versions of the N-end rule operate in mammals, yeast and bacteria (unpublished data). The N-end rule-based degradation signal comprises a destabilizing amino-terminal residue and a specific internal lysine residue. We now show that, in a multisubunit protein, these two determinants can be located on different subunits and still target the protein for destruction. Moreover, in this case (trans recognition) only the subunit that bears the lysine determinant is actually degraded. Thus an oligomeric protein can contain both short-lived and long-lived subunits. These insights have functional and practical implications.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: E S
authors.initials: ES
authors.lastname: Johnson
authors.forename: D K
authors.initials: DK
authors.lastname: Gonda
authors.forename: A
authors.initials: A
authors.lastname: Varshavsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006207:Half-Life; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D011506:Proteins; D014452:Ubiquitins; D013762:Tetrahydrofolate Dehydrogenase; D001616:beta-Galactosidase