Kinetic analysis of protein stability reveals age-dependent degradation

Erik McShane, Celine Sin, Henrick Zauber, Jonathan N. Wells, Neysan Donnelly, Xi Wang, Jingyi Hou, Wei Chen, Zuzana Storchova, Joseph A. Marsh, Angelo Valleriani, Matthias Selbach

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)803-815.e21
Number of pages25
Issue number3
Early online date6 Oct 2016
Publication statusPublished - 20 Oct 2016


Dive into the research topics of 'Kinetic analysis of protein stability reveals age-dependent degradation'. Together they form a unique fingerprint.

Cite this