Yang Wei, Paschen Wulf
Molecular Neurobiology Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.
Proteomics. 2015 Mar;15(5-6):1181-91. doi: 10.1002/pmic.201400298. Epub 2014 Oct 28.
Small ubiquitin-like modifier (SUMO1-3) conjugation is a posttranslational protein modification whereby SUMOs are conjugated to lysine residues of target proteins. SUMO conjugation can alter the activity, stability, and function of target proteins, and thereby modulate almost all major cellular pathways. Many diseases are associated with SUMO conjugation, including heart failure, arthritis, cancer, degenerative diseases, and brain ischemia/stroke. It is, therefore, of major interest to characterize the SUMO-modified proteome regulated by these disorders. SUMO proteomics analysis is hampered by low levels of SUMOylated proteins. Several strategies have, therefore, been developed to enrich SUMOylated proteins from cell/tissue extracts. These include proteomics analysis on cells expressing epitope-tagged SUMO isoforms, use of monoclonal SUMO antibodies for immunoprecipitation and epitope-specific peptides for elution, and affinity purification with peptides containing SUMO interaction motifs to specifically enrich polySUMOylated proteins. Recently, two mouse models were generated and characterized that express tagged SUMO isoforms, and allow purification of SUMOylated proteins from complex organ extracts. Ultimately, these new analytical tools will help to decipher the SUMO-modified proteome regulated by various human diseases, and thereby, identify new targets for preventive and therapeutic purposes.
小泛素样修饰物（SUMO1 - 3）缀合是一种蛋白质翻译后修饰，通过这种修饰，SUMO与靶蛋白的赖氨酸残基缀合。SUMO缀合可以改变靶蛋白的活性、稳定性和功能，从而调节几乎所有主要的细胞途径。许多疾病都与SUMO缀合有关，包括心力衰竭、关节炎、癌症、退行性疾病以及脑缺血/中风。因此，表征受这些疾病调节的SUMO修饰蛋白质组具有重大意义。SUMO蛋白质组学分析受到SUMO化蛋白质水平较低的阻碍。因此，已经开发了几种策略来从细胞/组织提取物中富集SUMO化蛋白质。这些策略包括对表达表位标签SUMO异构体的细胞进行蛋白质组学分析、使用单克隆SUMO抗体进行免疫沉淀以及使用表位特异性肽进行洗脱，以及用含有SUMO相互作用基序的肽进行亲和纯化以特异性富集多SUMO化蛋白质。最近，生成并表征了两种表达标签SUMO异构体的小鼠模型，它们能够从复杂的器官提取物中纯化SUMO化蛋白质。最终，这些新的分析工具将有助于解读受各种人类疾病调节的SUMO修饰蛋白质组，从而识别用于预防和治疗目的的新靶点。
