Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens.
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.
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Marko
M
Jovanovic
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Michael S
MS
Rooney
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Philipp
P
Mertins
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dariusz
D
Przybylski
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Harvard Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
Nicolas
N
Chevrier
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rahul
R
Satija
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA.
Edwin H
EH
Rodriguez
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA.
Alexander P
AP
Fields
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Schraga
S
Schwartz
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Raktima
R
Raychowdhury
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Maxwell R
MR
Mumbach
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Thomas
T
Eisenhaure
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Michal
M
Rabani
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dave
D
Gennert
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Diana
D
Lu
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Toni
T
Delorey
Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. Howard Hughes Medical Institute (HHMI), University of California, San Francisco, San Francisco, CA 94158, USA.
Jonathan S
JS
Weissman
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Steven A
SA
Carr
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. Harvard Medical School, Boston, MA 02115, USA. aregev@broad.mit.edu nhacohen@mgh.harvard.edu.
Nir
N
Hacohen
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA. HHMI, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA. aregev@broad.mit.edu nhacohen@mgh.harvard.edu.
Aviv
A
Regev
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007553:Isotope Labeling / Q000379:methods; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D014176:Protein Biosynthesis; D059748:Proteolysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017423:Sequence Analysis, RNA
D000596:Amino Acids; D008070:Lipopolysaccharides; D024101:Mitochondrial Proteins; D012333:RNA, Messenger