Protein synthesis rate is the predominant regulator of protein expression during differentiation

Mol Syst Biol. 2013:9:689. doi: 10.1038/msb.2013.47.

Abstract

External perturbations, by forcing cells to adapt to a new environment, often elicit large-scale changes in gene expression resulting in an altered proteome that improves the cell's fitness in the new conditions. Steady-state levels of a proteome depend on transcription, the levels of transcripts, translation and protein degradation but system-level contribution that each of these processes make to the final protein expression change has yet to be explored. We therefore applied a systems biology approach to characterize the regulation of protein expression during cellular differentiation using quantitative proteomics. As a general rule, it seems that protein expression during cellular differentiation is largely controlled by changes in the relative synthesis rate, whereas the relative degradation rate of the majority of proteins stays constant. In these data, we also observe that the proteins in defined sub-structures of larger protein complexes tend to have highly correlated synthesis and degradation rates but that this does not necessarily extend to the holo-complex. Finally, we provide strong evidence that the generally poor correlation observed between transcript and protein levels can fully be explained once the protein synthesis and degradation rates are taken into account.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Isotopes
  • Cell Differentiation
  • Cell Line
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Nitrogen Isotopes
  • Protein Biosynthesis / genetics*
  • Protein Multimerization
  • Proteolysis
  • Proteome / genetics*
  • Proteome / metabolism
  • Systems Biology

Substances

  • Carbon Isotopes
  • Nitrogen Isotopes
  • Proteome