Literature DB >> 21145464

Functional overlap and regulatory links shape genetic interactions between signaling pathways.

Sake van Wageningen1, Patrick Kemmeren, Philip Lijnzaad, Thanasis Margaritis, Joris J Benschop, Inês J de Castro, Dik van Leenen, Marian J A Groot Koerkamp, Cheuk W Ko, Antony J Miles, Nathalie Brabers, Mariel O Brok, Tineke L Lenstra, Dorothea Fiedler, Like Fokkens, Rodrigo Aldecoa, Eva Apweiler, Virginia Taliadouros, Katrin Sameith, Loes A L van de Pasch, Sander R van Hooff, Linda V Bakker, Nevan J Krogan, Berend Snel, Frank C P Holstege.   

Abstract

To understand relationships between phosphorylation-based signaling pathways, we analyzed 150 deletion mutants of protein kinases and phosphatases in S. cerevisiae using DNA microarrays. Downstream changes in gene expression were treated as a phenotypic readout. Double mutants with synthetic genetic interactions were included to investigate genetic buffering relationships such as redundancy. Three types of genetic buffering relationships are identified: mixed epistasis, complete redundancy, and quantitative redundancy. In mixed epistasis, the most common buffering relationship, different gene sets respond in different epistatic ways. Mixed epistasis arises from pairs of regulators that have only partial overlap in function and that are coupled by additional regulatory links such as repression of one by the other. Such regulatory modules confer the ability to control different combinations of processes depending on condition or context. These properties likely contribute to the evolutionary maintenance of paralogs and indicate a way in which signaling pathways connect for multiprocess control.
Copyright © 2010 Elsevier Inc. All rights reserved.

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Year:  2010        PMID: 21145464      PMCID: PMC3073509          DOI: 10.1016/j.cell.2010.11.021

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


  46 in total

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10.  Functional organization of the S. cerevisiae phosphorylation network.

Authors:  Dorothea Fiedler; Hannes Braberg; Monika Mehta; Gal Chechik; Gerard Cagney; Paromita Mukherjee; Andrea C Silva; Michael Shales; Sean R Collins; Sake van Wageningen; Patrick Kemmeren; Frank C P Holstege; Jonathan S Weissman; Michael-Christopher Keogh; Daphne Koller; Kevan M Shokat; Nevan J Krogan
Journal:  Cell       Date:  2009-03-06       Impact factor: 41.582

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  79 in total

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Journal:  Bioinformatics       Date:  2013-07-05       Impact factor: 6.937

6.  Ptc1 protein phosphatase 2C contributes to glucose regulation of SNF1/AMP-activated protein kinase (AMPK) in Saccharomyces cerevisiae.

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Review 7.  Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes.

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8.  Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae.

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9.  The genotype-phenotype map of yeast complex traits: basic parameters and the role of natural selection.

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10.  Quantification of degeneracy in biological systems for characterization of functional interactions between modules.

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