Show simple item record Módos, Dezső Brooks J Fazekas D Ari, Eszter Vellai, Tibor Csermely, Péter Korcsmáros, Tamás Földvári-Nagy Lászlóné Lenti, Katalin 2018-06-08T07:28:35Z 2018-06-08T07:28:35Z 2016
dc.identifier 85002410415
dc.identifier.citation pagination=38588, pages 13; journalVolume=6; journalTitle=SCIENTIFIC REPORTS;
dc.identifier.uri doi:10.1038/srep38588
dc.description.abstract Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis. 75 CPGs were found with higher degree, betweenness centrality, closeness, and 'bowtieness' when compared to other paralogs or other proteins in the signaling network. CPGs had higher diversity in all these measures, with more varied biological functions and more specific post-transcriptional regulation than non-critical paralog groups (non-CPG). Using TGF-beta, Notch and MAPK pathways as examples, SMAD2/3, NOTCH1/2/3 and MEK3/6-p38 CPGs were found to regulate the signaling flow of their respective pathways. Additionally, CPGs showed a higher mutation rate in both inherited diseases and cancer, and were enriched in drug targets. In conclusion, the results revealed two distinct types of paralog groups in the signaling network: CPGs and non-CPGs. Thus highlighting the importance of CPGs as compared to non-CPGs in drug discovery and disease pathogenesis.
dc.relation.ispartof urn:issn:2045-2322
dc.title Identification of critical paralog groups with indispensable roles in the regulation of signaling flow
dc.type Journal Article 2018-02-19T13:42:39Z
dc.language.rfc3066 en
dc.identifier.mtmt 3151362
dc.identifier.wos 000389299300001
dc.identifier.pubmed 27922122
dc.contributor.department SE/ETK2007/AEI/Morfológiai és Fiziológiai Tanszék
dc.contributor.department SE/AOK/I/Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet
dc.contributor.institution Semmelweis Egyetem

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