英国伦敦玛丽女王大学Pedro R. Cutillas研究团队,利用磷酸蛋白质组学数据重建的激酶网络拓扑结构揭示了与癌症相关的信号重连。该项研究成果2020年1月20日在线发表在《自然—生物技术》上。
Title: Reconstructing kinase network topologies from phosphoproteomics data reveals cancer-associated rewiring
Author: Maruan Hijazi, Ryan Smith, Vinothini Rajeeve, Conrad Bessant, Pedro R. Cutillas
Issue&Volume: 2020-01-20
Abstract: Understanding how oncogenic mutations rewire regulatory-protein networks is important for rationalizing the mechanisms of oncogenesis and for individualizing anticancer treatments. We report a chemical phosphoproteomics method to elucidate the topology of kinase-signaling networks in mammalian cells. We identified >6,000 protein phosphorylation sites that can be used to infer >1,500 kinase–kinase interactions and devised algorithms that can reconstruct kinase network topologies from these phosphoproteomics data. Application of our methods to primary acute myeloid leukemia and breast cancer tumors quantified the relationship between kinase expression and activity, and enabled the identification of hitherto unknown kinase network topologies associated with drug-resistant phenotypes or specific genetic mutations. Using orthogonal methods we validated that PIK3CA wild-type cells adopt MAPK-dependent circuitries in breast cancer cells and that the kinase TTK is important in acute myeloid leukemia. Our phosphoproteomic signatures of network circuitry can identify kinase topologies associated with both phenotypes and genotypes of cancer cells.
DOI: 10.1038/s41587-019-0391-9
Source: https://www.nature.com/articles/s41587-019-0391-9
Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex