Dynamic profiling of the protein life cycle in response to pathogens

Marko Jovanovic, Michael S. Rooney, Philipp Mertins, Dariusz Przybylski, Nicolas Chevrier, Rahul Satija, Edwin H. Rodriguez, Alexander P. Fields, Schraga Schwartz, Raktima Raychowdhury, Maxwell R. Mumbach, Thomas Eisenhaure, Michal Rabani, Dave Gennert, Diana Lu, Toni Delorey, Jonathan S. Weissman, Steven A. Carr, Nir Hacohen, Aviv Regev*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

332 Scopus citations

Abstract

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.

Original languageAmerican English
Article number1259038
JournalScience
Volume347
Issue number6226
DOIs
StatePublished - 6 Mar 2015
Externally publishedYes

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