Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Warren Alpert 536, Boston, MA 02115, USA.
Cell. 2013 Feb 28;152(5):1160-72. doi: 10.1016/j.cell.2013.02.007.
Ubiquitin and ubiquitin-like (Ubl) protein modifications affect protein stability, activity, and localization, but we still lack broad understanding of the functions of Ubl modifications. We have profiled the protein targets of ubiquitin and six additional Ubls in mitosis using a functional assay that utilizes active mammalian cell extracts and protein microarrays and identified 1,500 potential substrates; 80-200 protein targets were exclusive to each Ubl. The network structure is nonrandom, with most targets mapping to a single Ubl. There are distinct molecular functions for each Ubl, suggesting divergent biological roles. Analysis of differential profiles between mitosis and G1 highlighted a previously underappreciated role for the Ubl, FAT10, in mitotic regulation. In addition to its role as a resource for Ubl modifications, our study provides a systematic approach to analyze changes in posttranslational modifications at various cellular states.
泛素和泛素样（Ubl）蛋白修饰影响蛋白质的稳定性、活性和定位，但我们仍然缺乏对 Ubl 修饰功能的广泛了解。我们使用一种功能测定法，利用活性哺乳动物细胞提取物和蛋白质微阵列，对有丝分裂中的泛素和其他六种 Ubl 的蛋白质靶标进行了分析，鉴定出了 1500 个潜在的底物；每种 Ubl 都有 80-200 个蛋白靶标是独特的。网络结构是非随机的，大多数靶标都映射到单个 Ubl 上。每个 Ubl 都有不同的分子功能，表明其具有不同的生物学作用。有丝分裂和 G1 之间的差异分析突显了 Ubl、FAT10 在有丝分裂调控中的一个以前被低估的作用。除了作为 Ubl 修饰的来源之外，我们的研究还提供了一种系统的方法来分析各种细胞状态下的翻译后修饰变化。
