Abstract
The orchestration of protein production and degradation, and the regulation of protein lifetimes, play a central role in the majority of biological processes. Recent advances in proteomics have enabled the estimation of protein half-lives for thousands of proteins in vivo. What is the utility of these measurements, and how can they be leveraged to interpret the proteome changes occurring during development, aging, and disease? This opinion article summarizes leading technical approaches and highlights their strengths and weaknesses. We also disambiguate frequently used terminology, illustrate recent mechanistic insights, and provide guidance for interpreting and validating protein turnover measurements. Overall, protein lifetimes, coupled to estimates of protein levels, are essential for obtaining a deep understanding of mammalian biology and the basic processes defining life itself.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 106-118 |
| Number of pages | 13 |
| Journal | Trends in Biochemical Sciences |
| Volume | 48 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2023 |
Funding
We thank members of the laboratories of E.F.F. and J.N.S. for commenting the initial draft of this work. This work was supported by R01AG061787, R01AG061865, and R21AG072343 (J.N.S.) and by a Schram Stiftung ( T0287/35359/2020 ) and a Deutsche Forschungsgemeinschaft ( DFG ) grant ( FO 1342/1-3 ) to E.F.F. E.F.F. also acknowledges the support of the Collaborative Research Center 1286 on Quantitative Synaptologie ( CRC/SFB1286 ), Göttingen, Germany. We apologize to the colleagues whose works have not been cited owing to space limitations.
Keywords
- long-lived proteins
- metabolic labeling
- protein half-life
- protein turnover
- proteomics
- stable isotopes
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology