Kinetic Analysis of Protein Stability Reveals Age-Dependent Degradation

Cell. 2016 Oct 20;167(3):803-815.e21. doi: 10.1016/j.cell.2016.09.015. Epub 2016 Oct 6.


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.

Keywords: aneuploidy; bioorthogonal amino acid tagging; gene copy-number alterations; metabolic labeling; posttranslational control; protein complex assembly; protein degradation; proteomics; pulse chase experiment; trisomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / chemistry
  • Aneuploidy
  • Cell Line
  • Click Chemistry
  • Gene Amplification
  • Humans
  • Kinetics
  • Markov Chains
  • Proteasome Endopeptidase Complex / chemistry
  • Protein Biosynthesis
  • Protein Stability*
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteolysis*
  • Proteome
  • Ubiquitin / chemistry


  • Proteins
  • Proteome
  • Ubiquitin
  • azidohomoalanine
  • Proteasome Endopeptidase Complex
  • Alanine