The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Coordination of bacterial proteome with metabolism by cyclic AMP signalling
Open accessAbstract
The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.
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In the citing paper
“Supply-driven activation (and its dynamic counterpart, integral feedforward regulation) is used to balance flux among other modular networks such as nitrogen uptake (Kim et al, 2012), the metabolic regulation of glycolysis (Kochanowski et al, 2012), and carbon and nitrogen utilization (You et al, 2013).”
From Emergence of robust growth laws from optimal regulation of ribosome synthesis (2014) · cites this paper as You et al, 2013
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“Integral control has been implicated in the regulation of nitrogen uptake (Kim et al, 2012), and the coordination of nitrogen and carbon utilization (You et al, 2013)”
From Emergence of robust growth laws from optimal regulation of ribosome synthesis (2014) · cites this paper as You et al, 2013
In the citing paper
“On the contrary, empirical laws in biology may generally suggest the existence of underlying robust regulatory strategies and pinpoint their molecular implementations, as demonstrated recently for the problem of cAMP signaling that has evaded 50 years of genetic and high-throughput studies (You et al, 2013).”
From Emergence of robust growth laws from optimal regulation of ribosome synthesis (2014) · cites this paper as You et al, 2013
In the citing paper
“nevertheless, the interactions between cell growth and gene expression follow surprisingly simple rules in bacteria (Scott et al, 2010; You et al, 2013).”
From Emergence of robust growth laws from optimal regulation of ribosome synthesis (2014) · cites this paper as You et al, 2013
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Citations
Cites
Principles of c-di-GMP signalling in bacteria
Hengge, R. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2109 · Cited by 1,617
Interdependence of Cell Growth and Gene Expression: Origins and Consequences
Scott, M., Gunderson, C. W., Mateescu, E. M., Zhang, Z., & Hwa, T. (2010) · Science · doi:10.1126/science.1192588 · Cited by 1,470
Self-citationSchaechter, M., MaalOe, O., & Kjeldgaard, N. O. (1958) · Journal of General Microbiology · doi:10.1099/00221287-19-3-592 · Cited by 1,435
Deutscher, J., Francke, C., & Postma, P. W. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00024-06 · Cited by 1,411
Potrykus, K., & Cashel, M. (2008) · Annual Review of Microbiology · doi:10.1146/annurev.micro.62.081307.162903 · Cited by 1,170
TRANSCRIPTIONAL REGULATION BY cAMP AND ITS RECEPTOR PROTEIN
Kolb, A., Busby, S. J. W., BUC, H. C., Garges, S., & Adhya, S. L. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.003533 · Cited by 848
p53 Dynamics Control Cell Fate
Purvis, J. E., Karhohs, K. W., Mock, C., Batchelor, E., Loewer, A., & Lahav, G. (2012) · Science · doi:10.1126/science.1218351 · Cited by 770
Specificity in Two-Component Signal Transduction Pathways
Laub, M. T., & Goulian, M. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.042007.170548 · Cited by 752
Growth Rate-Dependent Global Effects on Gene Expression in Bacteria
Klumpp, S., Zhang, Z., & Hwa, T. (2009) · Cell · doi:10.1016/j.cell.2009.12.001 · Cited by 703
Self-citationCatabolite RepressionPreprint
Magasanik, B. (1961) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1961.026.01.031 · Cited by 537
Cited by
Sorted by citations
Li, G., Burkhardt, D. H., Gross, C. A., & Weissman, J. S. (2014) · Cell · doi:10.1016/j.cell.2014.02.033 · Cited by 1,259
Metabolomics and Isotope Tracing
Jang, C., Chen, L., & Rabinowitz, J. D. (2018) · Cell · doi:10.1016/j.cell.2018.03.055 · Cited by 841
Overflow metabolism in Escherichia coli results from efficient proteome allocation
Basan, M., Hui, S., Okano, H., Zhang, Z., Shen, Y., Williamson, J. R., & Hwa, T. (2015) · Nature · doi:10.1038/nature15765 · Cited by 785
Self-citationCoordination of microbial metabolism
Chubukov, V., Gerosa, L., Kochanowski, K., & Sauer, U. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3238 · Cited by 611
Emergence of robust growth laws from optimal regulation of ribosome synthesis
Scott, M., Klumpp, S., Mateescu, E. M., & Hwa, T. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145379 · Cited by 443
Self-citation
Metadata
- Authors
- You, C., Okano, H., Hui, S., Zhang, Z., Kim, M., Gunderson, C. W., Wang, Y.-P., Lenz, P., Yan, D., & Hwa, T.
- Affiliations
- University of California San Diego (US)
- Philipps University of Marburg (DE)
- Indiana University Indianapolis (US)
- Venue
- Nature
- Published
- 2013-08
- Volume
- 500
- Issue
- 7462
- Pages
- 301-306
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4038431
- OpenAlex
- W2044463066
- Cited by
- 432
- References
- 50
- Citations by year
- 2026: 32 · 2025: 37 · 2024: 28 · 2023: 32 · 2022: 36 · 2021: 36 · 2020: 29 · 2019: 36 · 2018: 31 · 2017: 26 · 2016: 22 · 2015: 42 · 2014: 34 · 2013: 11
- FWCI
- 24.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM095903)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- cAMP signaling, catabolite repression, Escherichia coli, growth rate dependence, biosynthetic gene expression, nitrogen limitation, sulfur limitation, integral feedback control, nutrient limitation, ribosomal proteins
- MeSH terms
- Cyclic AMP, Escherichia coli, Models, Biological, Signal Transduction, Gene Expression Regulation, Bacterial, Proteome, Escherichia coli Proteins
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