title: Kinetic Analysis of Protein Stability Reveals Age-Dependent Degradation.
abstract: Do young and old protein molecules have the same probability to be degraded? We addressed this question using metabolic pulse-chase labeling and quantitative mass spectrometry to obtain degradation profiles for thousands of proteins. We find that >10% of proteins are degraded non-exponentially. Specifically, proteins are less stable in the first few hours of their life and stabilize with age. Degradation profiles are conserved and similar in two cell types. Many non-exponentially degraded (NED) proteins are subunits of complexes that are produced in super-stoichiometric amounts relative to their exponentially degraded (ED) counterparts. Within complexes, NED proteins have larger interaction interfaces and assemble earlier than ED subunits. Amplifying genes encoding NED proteins increases their initial degradation. Consistently, decay profiles can predict protein level attenuation in aneuploid cells. Together, our data show that non-exponential degradation is common, conserved, and has important consequences for complex formation and regulation of protein abundance.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, 13092 Berlin, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: McShane
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: Celine
authors.initials: C
authors.lastname: Sin
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, 13092 Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zauber
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 3BB, UK.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Wells
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Neysan
authors.initials: N
authors.lastname: Donnelly
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, 13092 Berlin, Germany.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, 13092 Berlin, Germany.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hou
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, 13092 Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany; University of Kaiserslautern, Paul-Ehrlich Str. 24, 67663 Kaiserslautern, Germany.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Storchova
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 3BB, UK.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Marsh
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
authors.forename: Angelo
authors.initials: A
authors.lastname: Valleriani
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, 13092 Berlin, Germany; Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. Electronic address: matthias.selbach@mdc-berlin.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Selbach
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D000782:Aneuploidy; D002460:Cell Line; D057930:Click Chemistry; D005784:Gene Amplification; D006801:Humans; D007700:Kinetics; D008390:Markov Chains; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D014176:Protein Biosynthesis; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D020543:Proteome; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D011506:Proteins; D020543:Proteome; D025801:Ubiquitin; C506098:azidohomoalanine; D046988:Proteasome Endopeptidase Complex; D000409:Alanine
keywords: aneuploidy; bioorthogonal amino acid tagging; gene copy-number alterations; metabolic labeling; posttranslational control; protein complex assembly; protein degradation; proteomics; pulse chase experiment; trisomy