Dynamic profiling of the protein life cycle in response to pathogens

Protein expression is regulated by production and degradation of mRNAs and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics to build a quantitative genomic model of the differential regulation of gene expressio...

Full description

Bibliographic Details
Main Authors: Jovanovic, M., Mertins, P., Przybylski, D., Chevrier, N., Satija, R., Rodriguez, E. H., Fields, A. P., Schwartz, S., Raychowdhury, R., Mumbach, M. R., Eisenhaure, T., Rabani, M., Gennert, D., Lu, D., Delorey, T., Weissman, J. S., Carr, S. A., Hacohen, N., Regev, Aviv, Rooney, Michael Steven
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: American Association for the Advancement of Science (AAAS) 2016
Online Access:http://hdl.handle.net/1721.1/105732
https://orcid.org/0000-0001-8567-2049
_version_ 1811082525529866240
author Jovanovic, M.
Mertins, P.
Przybylski, D.
Chevrier, N.
Satija, R.
Rodriguez, E. H.
Fields, A. P.
Schwartz, S.
Raychowdhury, R.
Mumbach, M. R.
Eisenhaure, T.
Rabani, M.
Gennert, D.
Lu, D.
Delorey, T.
Weissman, J. S.
Carr, S. A.
Hacohen, N.
Regev, Aviv
Rooney, Michael Steven
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Jovanovic, M.
Mertins, P.
Przybylski, D.
Chevrier, N.
Satija, R.
Rodriguez, E. H.
Fields, A. P.
Schwartz, S.
Raychowdhury, R.
Mumbach, M. R.
Eisenhaure, T.
Rabani, M.
Gennert, D.
Lu, D.
Delorey, T.
Weissman, J. S.
Carr, S. A.
Hacohen, N.
Regev, Aviv
Rooney, Michael Steven
author_sort Jovanovic, M.
collection MIT
description Protein expression is regulated by production and degradation of mRNAs and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics to build a quantitative genomic model of the differential regulation of gene expression in LPS-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 over half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction of novel cellular functions and remodeling of preexisting functions through the protein life cycle.
first_indexed 2024-09-23T12:04:30Z
format Article
id mit-1721.1/105732
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T12:04:30Z
publishDate 2016
publisher American Association for the Advancement of Science (AAAS)
record_format dspace
spelling mit-1721.1/1057322022-09-27T23:59:02Z Dynamic profiling of the protein life cycle in response to pathogens Jovanovic, M. Mertins, P. Przybylski, D. Chevrier, N. Satija, R. Rodriguez, E. H. Fields, A. P. Schwartz, S. Raychowdhury, R. Mumbach, M. R. Eisenhaure, T. Rabani, M. Gennert, D. Lu, D. Delorey, T. Weissman, J. S. Carr, S. A. Hacohen, N. Regev, Aviv Rooney, Michael Steven Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Regev, Aviv Rooney, Michael Steven Protein expression is regulated by production and degradation of mRNAs and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics to build a quantitative genomic model of the differential regulation of gene expression in LPS-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 over half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction of novel cellular functions and remodeling of preexisting functions through the protein life cycle. National Human Genome Research Institute (U.S.) (Center for Excellence in Genomics Science P50 HG006193) Broad Institute of MIT and Harvard National Institutes of Health (U.S.) (Pioneer Award) Howard Hughes Medical Institute National Institutes of Health (U.S.) (Training Program in Bioinformatics and Integrative Genomics Training Grant) 2016-12-06T21:08:55Z 2016-12-06T21:08:55Z 2015-03 2014-07 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/105732 Jovanovic, M. et al. “Dynamic Profiling of the Protein Life Cycle in Response to Pathogens.” Science 347.6226 (2015): 1259038–1259038. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1126/science.1259038 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC
spellingShingle Jovanovic, M.
Mertins, P.
Przybylski, D.
Chevrier, N.
Satija, R.
Rodriguez, E. H.
Fields, A. P.
Schwartz, S.
Raychowdhury, R.
Mumbach, M. R.
Eisenhaure, T.
Rabani, M.
Gennert, D.
Lu, D.
Delorey, T.
Weissman, J. S.
Carr, S. A.
Hacohen, N.
Regev, Aviv
Rooney, Michael Steven
Dynamic profiling of the protein life cycle in response to pathogens
title Dynamic profiling of the protein life cycle in response to pathogens
title_full Dynamic profiling of the protein life cycle in response to pathogens
title_fullStr Dynamic profiling of the protein life cycle in response to pathogens
title_full_unstemmed Dynamic profiling of the protein life cycle in response to pathogens
title_short Dynamic profiling of the protein life cycle in response to pathogens
title_sort dynamic profiling of the protein life cycle in response to pathogens
url http://hdl.handle.net/1721.1/105732
https://orcid.org/0000-0001-8567-2049
work_keys_str_mv AT jovanovicm dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT mertinsp dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT przybylskid dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT chevriern dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT satijar dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT rodriguezeh dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT fieldsap dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT schwartzs dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT raychowdhuryr dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT mumbachmr dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT eisenhauret dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT rabanim dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT gennertd dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT lud dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT deloreyt dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT weissmanjs dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT carrsa dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT hacohenn dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT regevaviv dynamicprofilingoftheproteinlifecycleinresponsetopathogens
AT rooneymichaelsteven dynamicprofilingoftheproteinlifecycleinresponsetopathogens