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.

中文翻译：

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炎症衍生的髓样抑制细胞外囊泡中泛素结合的探测。

已经使用蛋白质组学方法研究了髓样抑制细胞（MDSC）释放的细胞外囊泡（EV）携带的泛素化蛋白，以检查肿瘤相关炎症的影响。从具有低和高炎症的荷瘤小鼠中分离后，直接从MDSC收集EV。在鉴定出的1092种蛋白（高炎症）和925种蛋白（低炎症）中，观察到50％以上是泛素化的蛋白形式。平均每个泛素化蛋白鉴定出三个以上的泛素附着位点。在促炎蛋白S100 A8和S100 A9中发现了多个泛素化位点，这是MDSC的特征，在其他蛋白中的组蛋白和转录调节剂中也有发现。光谱计数和途径分析表明泛素化独立于炎症而发生。研究表明，一些泛素化蛋白可导致MDSC迁移，而MDSC先前已与免疫抑制和肿瘤进展相关。最后，发现MDSC EV共同携带催化泛素化所需的所有酶，并且提出了假说的一部分泛素化蛋白质是在原位产生的。