Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Eiryo Kawakami, Vivek K Singh, Kazuko Matsubara, Takashi Ishii, Yukiko Matsuoka, Takeshi Hase, Priya Kulkarni, Kenaz Siddiqui, Janhavi Kodilkar, Nitisha Danve, Indhupriya Subramanian, Manami Katoh, Yuki Shimizu-Yoshida, Samik Ghosh, Abhay Jere, Hiroaki Kitano

ABSTRACT

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker's or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow-tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow-tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. More... »

PAGES

npjsba201518

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/npjsba.2015.18

DOI

http://dx.doi.org/10.1038/npjsba.2015.18

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050166320

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28725465


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