GPS-ARM: computational analysis of the APC/C recognition motif by predicting D-boxes and KEN-boxes.
GPS-ARM: computational analysis of the APC/C recognition motif by predicting D-boxes and KEN-boxes.
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GPS-ARM：通过预测 D-Box 和 KEN-Box 对 APC/C 识别基序进行计算分析
DOI：
10.1371/journal.pone.0034370
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xue Y
中科院分区：
文献类型：
--
作者：
Liu Z;Yuan F;Ren J;Cao J;Zhou Y;Yang Q;Xue Y
后期促进复合体/环体(APC/C)是一种与CDH1和/或CDC20结合的E3泛素连接酶，它识别并与特定底物相互作用，并通过靶向蛋白酶体降解蛋白来忠实地协调适当的细胞周期事件。APC/C底物的实验鉴定在很大程度上取决于APC/C识别基序的发现，例如D-box和Ken-box。尽管有一些严格或松散的主题被提出，但由于它们的预测能力不足，这些主题模式的使用有限。我们报道了一个新的GPS-ARM软件包的开发，它可以用于预测蛋白质中的D-盒和Ken-盒。使用实验识别的D盒和Ken盒作为训练数据集，采用了先前开发的基于组的预测系统(GPS)算法。通过广泛的评估和比较，发现GPS-ARM的性能比使用简单图案的要好得多。利用这一强大的工具，我们预测了智慧鱼3,832个蛋白质中的4,841个潜在D盒和1,403个蛋白质中的1,632个潜在Ken-box，而进一步的统计分析表明，D-box和Ken-box蛋白都参与了细胞周期以外的广泛生物学过程。此外，利用共定位信息，我们预测了数百个有丝分裂特异的APC/C底物。作为第一个预测APC/C介导的降解的计算工具，GPS-ARM是一个有用的信息工具，可用于进一步的实验研究。学术研究人员可在以下网址免费使用全球定位系统ARM：http://arm.biocuckoo.org.
Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase incorporated with Cdh1 and/or Cdc20 recognizes and interacts with specific substrates, and faithfully orchestrates the proper cell cycle events by targeting proteins for proteasomal degradation. Experimental identification of APC/C substrates is largely dependent on the discovery of APC/C recognition motifs, e.g., the D-box and KEN-box. Although a number of either stringent or loosely defined motifs proposed, these motif patterns are only of limited use due to their insufficient powers of prediction. We report the development of a novel GPS-ARM software package which is useful for the prediction of D-boxes and KEN-boxes in proteins. Using experimentally identified D-boxes and KEN-boxes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted. By extensive evaluation and comparison, the GPS-ARM performance was found to be much better than the one using simple motifs. With this powerful tool, we predicted 4,841 potential D-boxes in 3,832 proteins and 1,632 potential KEN-boxes in 1,403 proteins from H. sapiens, while further statistical analysis suggested that both the D-box and KEN-box proteins are involved in a broad spectrum of biological processes beyond the cell cycle. In addition, with the co-localization information, we predicted hundreds of mitosis-specific APC/C substrates with high confidence. As the first computational tool for the prediction of APC/C-mediated degradation, GPS-ARM is a useful tool for information to be used in further experimental investigations. The GPS-ARM is freely accessible for academic researchers at: http://arm.biocuckoo.org.
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