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Sebastian Gude et al. | Nature 578, 588-592 (2020) | pdf & DOI
Processive extrusion of polypeptide loops by a Hsp100 disaggregase
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Stochasticity of metabolism and growth at the single-cell level
Daniel J. Kiviet et al. | Nature 514, 376-379 (2014) | pdf & DOI: 10.1038/nature13582
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Tradeoffs and optimality in the evolution of gene regulation
Frank J. Poelwijk et al. | Cell 146, 462-470 (2011) | pdf & DOI:10.1016/j.cell.2011.06.035
Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway
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Douglas E. Smith, Sander J. Tans et al. | Nature 413:748-52 (2001) | pdf & DOI:10.1038/35099581
Molecular transistors: Potential modulations along carbon nanotubes
Sander J. Tans, Cees Dekker. | Nature 404:834-35 (2000) | pdf & DOI:10.1038/35009026
Imaging electron wave functions of quantized energy levels in carbon nanotubes
Liesbeth C. Venema et al. | Science 283:52-55 (1999) | pdf & DOI:10.1126/science.283.5398.52
Electron-electron correlations in carbon nanotubes
Sander J. Tans et al. | Nature 394:761-64 (1998) | pdf & DOI:10.1038/29494
Room-temperature transistor based on a single carbon nanotube
Sander J. Tans, Alwin R. M. Verschueren & Cees Dekker | Nature 393:49-52 (1998) | pdf & DOI:10.1038/29954
Individual single-wall carbon nanotubes as quantum wires
Sander J. Tans et al. | Nature 386:474-77 (1997) | pdf & DOI:10.1038/386474a0
Fullerene 'crop circles'
Jie Liu et al. | Nature 385, 780-781 (1997) | pdf & DOI:10.1038/385780b0

Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology

van Wijk, R.; Tans, S. J.; ten Wolde, P. R.; Mashaghi, A.
Abstract:
Currently, drug discovery approaches commonly assume a monotonic dose-response relationship. However, the assumption of monotonicity is increasingly being challenged. Here we show that for two simple interacting linear signaling pathways that carry two different signals with different physiological responses, a non-monotonic input-output relation can arise with simple network topologies including coherent and incoherent feed-forward loops. We show that non-monotonicity of the response functions has severe implications for pharmacological treatment. Fundamental constraints are imposed on the effectiveness and toxicity of any drug independent of its chemical nature and selectivity due to the specific network structure.
Year:
2015
Type of Publication:
Article
Journal:
Sci Rep
Volume:
5
Pages:
11376
Month:
June
Note:
[PubMed Central:\href{https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155565}{PMC5155565}] [DOI:\href{https://dx.doi.org/10.1038/srep11376}{10.1038/srep11376}] [PubMed:\href{https://www.ncbi.nlm.nih.gov/pubmed/26087464}{26087464}]
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