Global survey of endogenous substrates for Hero proteins upon proteostasis dysfunction and implication in anti-aggregation strategy.

用不同的化学诱导剂，如蛋白酶体抑制、自噬抑制和伴侣抑制等来模拟蛋白质的不平衡，诱导蛋白质聚集。在全球范围内对英雄蛋白进行了调查，以寻找它们的天然客户，以潜在地最大限度地减少通过它们的共同表达而形成的聚集。过滤捕捉法主要用于研究蛋白质组的整体聚集和聚集，而质谱学则拓展了蛋白质组的广泛研究。验证了可能与Hero蛋白共定位的热门聚集蛋白候选蛋白，如Hero9可能在稳定核仁中的候选蛋白以维持核糖体生物发生方面具有重要功能。这些聚集蛋白的哪些性质对Hero蛋白的解聚特性可能起重要作用仍是研究的主题。然而，在过滤捕获过程后，利用质谱仪研究了每个Hero蛋白(Hero7、Hero9、Hero11、Hero13、Hero20、Hero45)的其他聚集客户的数量。该技术是从经典的过滤捕获聚集体的方法本质上改进而来的，是以系统范围的方式研究聚集蛋白质的新方法。此外，未来的研究将暗示内源性蛋白稳定的机制，以解除其潜在的聚集和该蛋白的功能，防止生理障碍，如神经疾病。

Different chemical insults to mimic proteostatic disbalance such as Proteasome inhibition, autophagy inhibition and chaperone inhibition were used to induce the protein aggregation. Hero proteins were surveyed globally for their natural clients to potentially minimize the aggregation formation by their co-expression. Filter trap method was mostly used to investigate global aggregation and aggregating proteome wide study was extended by mass spectrometry. Top hit aggregating protein candidates which could be possibly co-localized with the Hero proteins were validated such as Hero9 might have essential function in stabilizing the candidate proteins in nucleolus to maintain the ribosome biogenesis. It is still the subject of study what properties of these aggregating proteins could be important for the action of Hero proteins for their disaggregation properties.Yet number of other aggregating clients for each of the Hero proteins (Hero7, Hero9, Hero11, Hero13, Hero20, Hero45) were studied upon proteasome inhibition system-wide utilizing mass spectrometry after the filter trapping process. This technique is novel approach to study the aggregating proteins in system-wide manner which is essentially modified from the classical technique of filter trapping the aggregates. Further, the future study will imply for the mechanism of endogenous protein stabilization to relieve their potential aggregation and functionality of that proteins preventing the physiological disorders such as neurological disorders.