Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens

Science. 2015 Mar 6;347(6226):1259038. doi: 10.1126/science.1259038. Epub 2015 Feb 12.


Protein expression is regulated by the production and degradation of messenger RNAs (mRNAs) and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics so as to build a quantitative genomic model of the differential regulation of gene expression in lipopolysaccharide-stimulated mouse dendritic cells. Changes in mRNA abundance play a dominant role in determining most dynamic fold changes in protein levels. Conversely, the preexisting proteome of proteins performing basic cellular functions is remodeled primarily through changes in protein production or degradation, accounting for more than half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction for newly activated cellular functions and by protein life-cycle changes for remodeling of preexisting functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Animals
  • Bone Marrow Cells / immunology*
  • Cell Culture Techniques
  • Dendritic Cells / immunology*
  • Host-Pathogen Interactions / immunology*
  • Isotope Labeling / methods
  • Lipopolysaccharides / immunology
  • Mice
  • Mitochondrial Proteins / metabolism
  • Molecular Dynamics Simulation*
  • Protein Biosynthesis*
  • Proteolysis*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Sequence Analysis, RNA


  • Amino Acids
  • Lipopolysaccharides
  • Mitochondrial Proteins
  • RNA, Messenger

Associated data

  • GEO/GSE59793