Cell growth and cell cycle in Saccharomyces cerevisiae: Basic regulatory design and protein–protein interaction network

Alberghina, Lilia; Mavelli, Gabriella; Drovandi, Guido; Palumbo, Pasquale; Pessina, S.; Tripodi, Farida; Coccetti, Paola; Vanoni, Marco

doi:10.1016/j.biotechadv.2011.07.010

Cited by 49 publications

(54 citation statements)

References 239 publications

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“…These are highly characterized and strongly interacting networks and the connection between these processes is of high importance in other organisms [7], [13], [80]–[82]. We confirmed that many of the highest linkerity scoring proteins in the polarity network were already known to play important roles in multiple processes.…”

Section: Discussionsupporting

confidence: 73%

“…Very recent network predictions based on machine-learning methods [33] will enable us to perform more careful analysis in this organism as well. Other organisms with larger gene sets will often have a lower annotation coverage [96]; in these cases functional groups in the PPI network need to be identified by community detection algorithms or predefined by the authors [80]. Once such functional groups are established, the described method provides a good means to identify proteins likely to have a role in connecting functional regulatory networks in any organism.…”

Section: Discussionmentioning

confidence: 99%

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Linkers of Cell Polarity and Cell Cycle Regulation in the Fission Yeast Protein Interaction Network

et al. 2012

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The study of gene and protein interaction networks has improved our understanding of the multiple, systemic levels of regulation found in eukaryotic and prokaryotic organisms. Here we carry out a large-scale analysis of the protein-protein interaction (PPI) network of fission yeast (Schizosaccharomyces pombe) and establish a method to identify ‘linker’ proteins that bridge diverse cellular processes - integrating Gene Ontology and PPI data with network theory measures. We test the method on a highly characterized subset of the genome consisting of proteins controlling the cell cycle, cell polarity and cytokinesis and identify proteins likely to play a key role in controlling the temporal changes in the localization of the polarity machinery. Experimental inspection of one such factor, the polarity-regulating RNB protein Sts5, confirms the prediction that it has a cell cycle dependent regulation. Detailed bibliographic inspection of other predicted ‘linkers’ also confirms the predictive power of the method. As the method is robust to network perturbations and can successfully predict linker proteins, it provides a powerful tool to study the interplay between different cellular processes.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Linkers of Cell Polarity and Cell Cycle Regulation in the Fission Yeast Protein Interaction Network

et al. 2012

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“…In conclusion, analysis at different zoom levels (analysis of structured and unstructured regions, interactome analysis), coupled to selected experiments allows to integrate previous information on Whi5, highlighting the importance of a multi-scale approach for a full understanding of complex biological functions (Kitano, 2010; Alberghina et al, 2012). The importance of combining structural data in functional protein network analysis has been recently highlighted (Kiel et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…In the budding yeast Saccharomyces cerevisiae , such a regulatory step takes place in the unbudded, G1 phase of the cell cycle, at a regulatory area termed START (Pringle and Hartwell, 1981). At START cellular parameters (i.e., the metabolic state) and environmental factors, including nutrient availability (Lord and Wheals, 1980; Vanoni et al, 1983; Searle and Sanchez, 2004; Youk and van Oudenaarden, 2009; Busti et al, 2010; Gutteridge et al, 2010) and mating pheromones (Cross and McKinney, 1992), are integrated and contribute to the cells decision to divide, or to differentiate in a resting state (Alberghina et al, 2012). In higher eukaryotes, the Restriction Point (Pardee, 1974) similarly integrates environmental signals, notably including growth factors, and its dysregulation results in abnormal cell cycle and development of proliferative disorders (Pardee, 1989; Sherr, 1996).…”

Section: Introductionmentioning

confidence: 99%

A comparative study of Whi5 and retinoblastoma proteins: from sequence and structure analysis to intracellular networks

et al. 2014

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Cell growth and proliferation require a complex series of tight-regulated and well-orchestrated events. Accordingly, proteins governing such events are evolutionary conserved, even among distant organisms. By contrast, it is more singular the case of “core functions” exerted by functional analogous proteins that are not homologous and do not share any kind of structural similarity. This is the case of proteins regulating the G1/S transition in higher eukaryotes–i.e., the retinoblastoma (Rb) tumor suppressor Rb—and budding yeast, i.e., Whi5. The interaction landscape of Rb and Whi5 is quite large, with more than one hundred proteins interacting either genetically or physically with each protein. The Whi5 interactome has been used to construct a concept map of Whi5 function and regulation. Comparison of physical and genetic interactors of Rb and Whi5 allows highlighting a significant core of conserved, common functionalities associated with the interactors indicating that structure and function of the network—rather than individual proteins—are conserved during evolution. A combined bioinformatics and biochemical approach has shown that the whole Whi5 protein is highly disordered, except for a small region containing the protein family signature. The comparison with Whi5 homologs from Saccharomycetales has prompted the hypothesis of a modular organization of structural disorder, with most evolutionary conserved regions alternating with highly variable ones. The finding of a consensus sequence points to the conservation of a specific phosphorylation rhythm along with two disordered sequence motifs, probably acting as phosphorylation-dependent seeds in Whi5 folding/unfolding. Thus, the widely disordered Whi5 appears to act as a hierarchical, “date hub” that has evolutionary assayed an original way of modular organization before being supplanted by the globular, multi-domain structured Rb, more suitable to cover the role of a “party hub”.

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“…1-3 for extensive review). Nutrients, and in particular glucose, influence the yeast cell metabolic behavior through the activation of signaling pathways, which in turn finely tune transcription and enzymatic activities (4), as well as cell growth and cell cycle (5).…”

mentioning

confidence: 99%

Snf1 Phosphorylates Adenylate Cyclase and Negatively Regulates Protein Kinase A-dependent Transcription in Saccharomyces cerevisiae

Nicastro

Tripodi

Gaggini

et al. 2015

Journal of Biological Chemistry

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Background:The Snf1/AMPK and PKA pathways are crucial for nutrient sensing and utilization in yeast. Results: A novel cross-talk mechanism between Snf1/AMPK and PKA is proposed. Conclusion: Snf1 and Cyr1 interact in a nutrient-independent manner. Active Snf1 phosphorylates Cyr1 and negatively regulates cAMP content and PKA-dependent transcription. Significance: This is the first evidence of regulation of PKA pathway by Snf1/AMPK.

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Cell growth and cell cycle in Saccharomyces cerevisiae: Basic regulatory design and protein–protein interaction network

Cited by 49 publications

References 239 publications

Linkers of Cell Polarity and Cell Cycle Regulation in the Fission Yeast Protein Interaction Network

Linkers of Cell Polarity and Cell Cycle Regulation in the Fission Yeast Protein Interaction Network

A comparative study of Whi5 and retinoblastoma proteins: from sequence and structure analysis to intracellular networks

Snf1 Phosphorylates Adenylate Cyclase and Negatively Regulates Protein Kinase A-dependent Transcription in Saccharomyces cerevisiae

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