伴侣作为细胞网络的整合者：应激和疾病中细胞完整性的变化
Chaperones as integrators of cellular networks: Changes of cellular integrity in stress and diseases
摘要：
细胞网络在压力和疾病期间经历重排。在非应激状态下，酵母蛋白质相互作用网络（相互作用组）是高度紧凑的，并且中心组织的模块具有大的重叠。在应力期间，几个原始模块变得更加分离，并且还出现了一些新的模块。一些基本功能，如蛋白酶体，保持其中心地位。然而，一些高能量需求的功能，如细胞周期调节，在应激期间失去了它们原来的中心性。许多关键的应激依赖性蛋白质复合物，如解聚特异性伴侣蛋白HSP 104，在应激酵母相互作用组中获得中心地位。分子伴侣、热休克蛋白或应激蛋白彼此之间以及与它们的伴侣之间形成复杂的相互作用网络（分子伴侣组）。在这里，我们表明，人类分子伴侣恢复分离蛋白质合成偶联和压力相关的分子伴侣最近在酵母中观察到。对酵母和人类相互作用组的研究表明，（1）分子伴侣是蛋白质相互作用网络的模块间整合剂，（2）通常桥接枢纽和（3）是广泛磷酸化的最佳候选者。此外，分子伴侣（4）在应激酵母蛋白质相互作用网络的分离模块的组织中变得更加中心，这突出了它们在应激期间和之后网络模块的去偶联和再偶联中的重要性。分子伴侣介导的细胞网络的进化性可能在应激和各种多基因和慢性疾病（如癌症、糖尿病或神经退行性疾病）期间的细胞适应中发挥关键作用。
英文摘要：
Cellular networks undergo rearrangements during stress and diseases. In un-stressed state the yeast protein-protein interaction network (interactome) is highly compact, and the centrally organized modules have a large overlap. During stress several original modules became more separated, and a number of novel modules also appear. A few basic functions, such as the proteasome preserve their central position. However, several functions with high energy demand, such the cell-cycle regulation loose their original centrality during stress. A number of key stress-dependent protein complexes, such as the disaggregation-specific chaperone, Hsp104, gain centrality in the stressed yeast interactome. Molecular chaperones, heat shock, or stress proteins form complex interaction networks (the chaperome) with each other and their partners. Here we show that the human chaperome recovers the segregation of protein synthesis-coupled and stress-related chaperones observed in yeast recently. Examination of yeast and human interactomes shows that (1) chaperones are inter-modular integrators of protein-protein interaction networks, which (2) often bridge hubs and (3) are favorite candidates for extensive phosphorylation. Moreover, chaperones (4) become more central in the organization of the isolated modules of the stressed yeast protein-protein interaction network, which highlights their importance in the de-coupling and re-coupling of network modules during and after stress. Chaperone-mediated evolvability of cellular networks may play a key role in cellular adaptation during stress and various polygenic and chronic diseases, such as cancer, diabetes or neurodegeneration.
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