Network motifs: theory and experimental approaches

Alon, Uri

doi:10.1038/nrg2102

Cited by 2,921 publications

(3,004 citation statements)

References 97 publications

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“…Akt achieves its function of phosphorylating to regulating FOXO proteins though the interaction with various factors that form a complex loop (30). PKR-like ER kinase (PERK) phosphorylates FOXO1 at Ser298, Ser301 and Ser303, but prefers Ser298 site, which is not a target of Akt.…”

Section: Phosphorylation Of Foxo Proteinsmentioning

confidence: 99%

Post-translational modifications of FOXO family proteins

Wang

Huang

2016

Molecular Medicine Reports

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Abstract. The Forkhead box O (FOXO) protein family is predominantly involved in apoptosis, oxidative stress, DNA damage/repair, tumor angiogenesis, glycometabolism, regulating life span and other important biological processes. Its activity is affected by a variety of posttranslational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, methylation and glycosylation. When cells are subjected to different environments, the corresponding PTMs act on the FOXO protein family, to change transcriptional activity or subcellular localization, and the expression of downstream target genes, will ultimately affect the biological behavior of the cells. In this review, we will discuss the biological characteristics of FOXO protein PTMs.

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Section: Phosphorylation Of Foxo Proteinsmentioning

confidence: 99%

Post-translational modifications of FOXO family proteins

Wang

Huang

2016

Molecular Medicine Reports

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“…Several studies have made contributions towards identifying some design principles for oscillatory behaviour. Network motifs-recurrent patterns of interactions believed to form the building blocks of any complex network (Milo et al 2002;Yeger-Lotem et al 2004;Barabasi and Oltvai 2004;Alon 2007;Kim et al 2010)-have also been highlighted to some extent for oscillators (Ferrell et al 2011;Wagner 2005;Novak and Tyson 2008;Tsai et al 2008;Burda et al 2011;Lomnitz and Savageau 2014;Noman et al 2015;Semenov et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Design principles for robust oscillatory behavior

2015

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Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems.

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“…FFLs can be generated with different combinations of activation‐inhibition pathways and are discussed in more details in refs. 16, 17, 18 Figure 1 d shows sigmoidal and biphasic input‐output relationship for coherent and incoherent FFLs, respectively.…”

Section: Immune System and Its Complexitymentioning

confidence: 99%

Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling

Rahman

Tiwari

Narula

et al. 2018

CPT Pharmacom & Syst Pharma

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The human adaptive immune system is a very complex network of different types of cells, cytokines, and signaling molecules. This complex network makes it difficult to understand the system level regulations. To properly explain the immune system, it is necessary to explicitly investigate the presence of different feedback and feedforward loops (FFLs) and their crosstalks. Considering that these loops increase the complexity of the system, the mathematical modeling has been proved to be an important tool to explain such complex biological systems. This review focuses on these regulatory loops and discusses their importance on systems modeling of the immune system.

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Network motifs: theory and experimental approaches

Cited by 2,921 publications

References 97 publications

Post-translational modifications of FOXO family proteins

Post-translational modifications of FOXO family proteins

Design principles for robust oscillatory behavior

Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling

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