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. 2012;7(3):e34370.
doi: 10.1371/journal.pone.0034370. Epub 2012 Mar 29.

GPS-ARM: Computational Analysis of the APC/C Recognition Motif by Predicting D-boxes and KEN-boxes

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Free PMC article

GPS-ARM: Computational Analysis of the APC/C Recognition Motif by Predicting D-boxes and KEN-boxes

Zexian Liu et al. PLoS One. .
Free PMC article

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The Sequence logos of ARM(2, 6) and ARM(8, 15) were generated by the HMM-Logo (LogoMat-M) for the (A) D-box and (B) KEN-box, respectively.
Figure 2
Figure 2. Screen snapshot of the GPS-ARM 1.0 software.
The default thresholds were chosen for the D-box (high) and KEN-box (low). As an example, the prediction results for the human centromere protein F/CENP-F (UniProt ID: P49454) are shown.
Figure 3
Figure 3. The prediction performance of GPS-ARM 1.0.
The LOO validation and 4-, 6-, 8- and 10-fold cross-validations were performed for (A) the D-box and (B) the KEN-box.

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References

    1. Milestones in cell division. Nat Cell Biol. 2001;3:E265. - PubMed
    1. Nasmyth K. A prize for proliferation. Cell. 2001;107:689–701. - PubMed
    1. Barford D. Structure, function and mechanism of the anaphase promoting complex (APC/C). Q Rev Biophys. 2011;44:153–190. - PubMed
    1. Thornton BR, Toczyski DP. Precise destruction: an emerging picture of the APC. Genes Dev. 2006;20:3069–3078. - PubMed
    1. Peters JM. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol. 2006;7:644–656. - PubMed

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