Department of Physics, State University of New York (SUNY) at Buffalo, Buffalo, NY 14260, USA.
Department of Physics, State University of New York (SUNY) at Buffalo, Buffalo, NY 14260, USA.
Trends Cell Biol. 2022 Aug;32(8):681-695. doi: 10.1016/j.tcb.2022.03.005. Epub 2022 Apr 25.
Biomolecular condensates are membraneless organelles (MLOs) that are enriched in specific proteins and nucleic acids, compartmentalized to perform biochemical functions. Such condensates are formed by phase separation (PS) enabled by protein domains that allow multivalent interactions. Chromosomal translocation-derived in-frame gene fusions often generate proteins with non-native domain combinations that rewire protein-protein interaction networks. Several recent studies have shown that, for a subset of these fusion proteins, pathogenesis can be driven by the ability of the fusion protein to undergo phase transitions at non-physiological cellular locations to form ectopic condensates. We highlight how such ectopic phase transitions can alter biological processes and posit that dysfunction via protein PS at non-physiological locations represents a generic route to oncogenic transformation.
生物分子凝聚物是无膜细胞器 (MLOs)，富含特定的蛋白质和核酸，分隔开来以执行生化功能。这种凝聚物是由允许多价相互作用的蛋白质结构域促成的相分离 (PS) 形成的。染色体易位衍生的框内基因融合经常产生具有非天然结构域组合的蛋白质，这些蛋白质重新连接蛋白质-蛋白质相互作用网络。最近的几项研究表明，对于这些融合蛋白中的一部分，融合蛋白在非生理细胞位置发生相转变以形成异位凝聚物的能力可以驱动发病机制。我们强调了这种异位相变如何改变生物过程，并假设非生理位置的蛋白质 PS 功能障碍代表致癌转化的一种通用途径。
