You are here

Science DOI:10.1126/science.1259038

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

Publication TypeJournal Article
Year of Publication2015
AuthorsJovanovic, M, Rooney, MS, Mertins, P, Przybylski, D, Chevrier, N, Satija, R, Rodriguez, EH, Fields, AP, Schwartz, S, Raychowdhury, R, Mumbach, MR, Eisenhaure, T, Rabani, M, Gennert, D, Lu, D, Delorey, T, Weissman, JS, Carr, SA, Hacohen, N, Regev, A
Date Published2015 Mar 06
KeywordsAmino Acids, Animals, Bone Marrow Cells, Cell Culture Techniques, Dendritic Cells, Host-Pathogen Interactions, Isotope Labeling, Lipopolysaccharides, Mice, Mitochondrial Proteins, Molecular Dynamics Simulation, Protein Biosynthesis, Proteolysis, RNA, Messenger, Sequence Analysis, RNA

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.


Alternate JournalScience
PubMed ID25745177
PubMed Central IDPMC4506746
Grant ListF32 HD075541 / HD / NICHD NIH HHS / United States
T32 GM008284 / GM / NIGMS NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States