Dynamic profiling of the protein life cycle in response to pathogens

被引：348

作者：

Jovanovic, Marko ^{[1
]}

Rooney, Michael S. ^{[1
,2
]}

Mertins, Philipp ^{[1
]}

Przybylski, Dariusz ^{[1
]}

Chevrier, Nicolas ^{[1
,3
]}

Satija, Rahul ^{[1
]}

Rodriguez, Edwin H. ^{[4
]}

Fields, Alexander P. ^{[4
]}

Schwartz, Schraga ^{[1
]}

Raychowdhury, Raktima ^{[1
]}

Mumbach, Maxwell R. ^{[1
]}

Eisenhaure, Thomas ^{[1
,5
]}

Rabani, Michal ^{[1
]}

Gennert, Dave ^{[1
]}

Lu, Diana ^{[1
]}

Delorey, Toni ^{[1
]}

Weissman, Jonathan S. ^{[4
,6
]}

Carr, Steven A. ^{[1
]}

Hacohen, Nir ^{[1
,5
,7
]}

Regev, Aviv ^{[1
,8
,9
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[3] Harvard Univ, Harvard Fac Arts & Sci, Ctr Syst Biol, Cambridge, MA 02138 USA

[4] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA

[5] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[6] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA

[7] Harvard Univ, Sch Med, Boston, MA 02115 USA

[8] MIT, Dept Biol, Cambridge, MA 02140 USA

[9] MIT, Dept Biol, HHMI, Cambridge, MA 02140 USA

来源：

SCIENCE | 2015年 / 347卷 / 6226期

基金：

瑞士国家科学基金会;

关键词：

MESSENGER-RNA; TEMPORAL DYNAMICS; DENDRITIC CELLS; REVEALS; EXPRESSION; TRANSLATION; PRINCIPLES; ABUNDANCE; TLR; QUANTIFICATION;

D O I：

10.1126/science.1259038

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

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