Identification of Novel Components of Target-of-Rapamycin Signaling Pathway by Network-Based Multi-Omics Integrative Analysis
| Autor: | Emir Erkol, Betul Kirdar, Duygu Dikicioglu, Arzu Celik, Barbara Di Camillo, Elif Dereli Eke, Kazim Yalcin Arga, Serpil Eraslan |
|---|---|
| Přispěvatelé: | Eke, Elif Dereli, Arga, Kazim Yalcin, Dikicioglu, Duygu, Eraslan, Serpil, Erkol, Emir, Celik, Arzu, Kirdar, Betul, Di Camillo, Barbara, Dikicioglu, Duygu [0000-0002-3018-4790], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteomics Saccharomyces cerevisiae Proteins INFORMATION DATABASE Saccharomyces cerevisiae Regulator Computational biology Mechanistic Target of Rapamycin Complex 2 Biology METABOLISM Mechanistic Target of Rapamycin Complex 1 Biochemistry biomarkers caffeine drug targets multiomics network-based analysis target of rapamycin (TOR) signaling Transcriptome 03 medical and health sciences 0302 clinical medicine ENHANCEMENT TOR FUNCTION Interaction network REVEALS Genetics TOR complex Molecular Biology MTORC2 Effector TOR Serine-Threonine Kinases biology.organism_classification TOR signaling 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine GROWTH AUTOPHAGY COMPLEXES Signal transduction Biotechnology Signal Transduction |
| DOI: | 10.17863/cam.39503 |
| Popis: | Target of rapamycin (TOR) is a major signaling pathway and regulator of cell growth. TOR serves as a hub of many signaling routes, and is implicated in the pathophysiology of numerous human diseases, including cancer, diabetes, and neurodegeneration. Therefore, elucidation of unknown components of TOR signaling that could serve as potential biomarkers and drug targets has a great clinical importance. In this study, our aim is to integrate transcriptomics, interactomics, and regulomics data in Saccharomyces cerevisiae using a network-based multiomics approach to enlighten previously unidentified, potential components of TOR signaling. We constructed the TOR-signaling protein interaction network, which was used as a template to search for TOR-mediated rapamycin and caffeine signaling paths. We scored the paths passing from at least one component of TOR Complex 1 or 2 (TORC1/TORC2) using the co-expression levels of the genes in the transcriptome data of the cells grown in the presence of rapamycin or caffeine. The resultant network revealed seven hitherto unannotated proteins, namely, Atg14p, Rim20p, Ret2p, Spt21p, Ylr257wp, Ymr295cp, and Ygr017wp, as potential components of TOR-mediated rapamycin and caffeine signaling in yeast. Among these proteins, we suggest further deciphering of the role of Ylr257wp will be particularly informative in the future because it was the only protein whose removal from the constructed network hindered the signal transduction to the TORC1 effector kinase Npr1p. In conclusion, this study underlines the value of network-based multiomics integrative data analysis in discovering previously unidentified components of the signaling networks by revealing potential components of TOR signaling for future experimental validation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|