| Modeling the Pathological Long-Range Regulatory Effects of Human Structural Variation with Patient-Specific hiPSCs | | Modeling the Pathological Long-Range Regulatory Effects of Human Structural Variation with Patient-Specific hiPSCs | Laugsch M, Bartusel M, Rehimi R, Alirzayeva H, Karaolidou A, Crispatzu G, Zentis P, Nikolic M, Bleckwehl T, Kolovos P, van Ijcken WFJ, Šarić T, Koehler K, Frommolt P, Lachlan K, Baptista J, Rada-Iglesias A. | 2019-05-01T22:00:00Z | <h3 style="margin:0px;font-weight:inherit;font-family:"yanone kaffeesatz";color:#96a9b5;font-size:1.25em;padding:0px;border:0px;font-stretch:inherit;vertical-align:baseline;background-color:#ffffff;">Abstract</h3><p style="padding:0px;border:0px;font-stretch:inherit;font-size:18px;font-family:"yanone kaffeesatz";vertical-align:baseline;color:#474f51;background-color:#ffffff;"></p><p style="padding:0px;border:0px;font-stretch:inherit;font-size:18px;font-family:"yanone kaffeesatz";vertical-align:baseline;color:#474f51;background-color:#ffffff;">Modern omics technologies allow us to obtain global information on different types of biological networks. However, integrating these different types of analyses into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics, and transcriptomics data. Applying this method to analyze HRAS signaling from different subcellular compartments shows that spatially defined networks contribute specific functions to HRAS signaling. Changes in HRAS protein interactions at different sites lead to different kinase activation patterns that differentially regulate gene transcription. HRAS-mediated signaling is the strongest from the cell membrane, but it regulates the largest number of genes from the endoplasmic reticulum. The integrated networks provide a topologically and functionally resolved view of HRASsignaling. They reveal distinct HRAS functions including the control of cell migration from the endoplasmic reticulum and TP53-dependent cell survival when signaling from the Golgi apparatus.<br></p><p></p> | <p><a href="https://www.sciencedirect.com/science/article/pii/S1934590919301031?via%3Dihub" style="color:#ed391b;margin:0px;padding:0px;border:0px;font-stretch:inherit;font-size:18px;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;background-color:#ffffff;">Cell Stem Cell</a><span style="color:#474f51;font-family:"yanone kaffeesatz";font-size:18px;background-color:#ffffff;">. 2019 May 2;24(5):736-752.e12. doi: 10.1016/j.stem.2019.03.004. Epub 2019 Apr 11.</span><br></p> | 234 | | |
