Department of Biological Sciences, University of Maryland, Baltimore County , Baltimore, Maryland 21250, United States.
Proteomic Core Facility, College of Mathematics and Natural Sciences, University of Maryland , College Park, Maryland 20742, United States.
J Proteome Res. 2018 Jan 5;17(1):315-324. doi: 10.1021/acs.jproteome.7b00585. Epub 2017 Nov 10.
Ubiquitinated proteins carried by the extracellular vesicles (EV) released by myeloid-derived suppressor cells (MDSC) have been investigated using proteomic strategies to examine the effect of tumor-associated inflammation. EV were collected from MDSC directly following isolation from tumor-bearing mice with low and high inflammation. Among the 1092 proteins (high inflammation) and 925 proteins (low inflammation) identified, more than 50% were observed as ubiquitinated proteoforms. More than three ubiquitin-attachment sites were characterized per ubiquitinated protein, on average. Multiple ubiquitination sites were identified in the pro-inflammatory proteins S100 A8 and S100 A9, characteristic of MDSC and in histones and transcription regulators among other proteins. Spectral counting and pathway analysis suggest that ubiquitination occurs independently of inflammation. Some ubiquitinated proteins were shown to cause the migration of MDSC, which has been previously connected with immune suppression and tumor progression. Finally, MDSC EV are found collectively to carry all the enzymes required to catalyze ubiquitination, and the hypothesis is presented that a portion of the ubiquitinated proteins are produced in situ.
髓系来源的抑制细胞（MDSC）释放的细胞外囊泡（EV）所携带的泛素化蛋白已通过蛋白质组学策略进行了研究，以研究与肿瘤相关的炎症的影响。EV 是从小鼠肿瘤中直接分离的 MDSC 中收集的，这些小鼠的炎症程度低和高。在所鉴定的 1092 种蛋白质（高炎症）和 925 种蛋白质（低炎症）中，超过 50％被观察为泛素化蛋白形式。平均而言，每个泛素化蛋白都有三个以上的泛素附着位点。在促炎蛋白 S100A8 和 S100A9 中鉴定出多个泛素化位点，这是 MDSC 的特征，在组蛋白和转录调节剂等其他蛋白中也存在泛素化。光谱计数和途径分析表明，泛素化的发生与炎症无关。一些泛素化蛋白可导致 MDSC 迁移，这与免疫抑制和肿瘤进展有关。最后，发现 MDSC EV 总共携带催化泛素化所需的所有酶，并且提出了一个假设，即一部分泛素化蛋白是原位产生的。
