Systematic Analysis and Prediction of In Situ Cross Talk of O-GlcNAcylation and Phosphorylation.

Heming Yao,Minghui Wang,Ao Li

doi:10.1155/2015/279823

Abstract

Reversible posttranslational modification (PTM) plays a very important role in biological process by changing properties of proteins. As many proteins are multiply modified by PTMs, cross talk of PTMs is becoming an intriguing topic and draws much attention. Currently, lots of evidences suggest that the PTMs work together to accomplish a specific biological function. However, both the general principles and underlying mechanism of PTM crosstalk are elusive. In this study, by using large-scale datasets we performed evolutionary conservation analysis, gene ontology enrichment, motif extraction of proteins with cross talk of O-GlcNAcylation and phosphorylation cooccurring on the same residue. We found that proteins with in situ O-GlcNAc/Phos cross talk were significantly enriched in some specific gene ontology terms and no obvious evolutionary pressure was observed. Moreover, 3 functional motifs associated with O-GlcNAc/Phos sites were extracted. We further used sequence features and GO features to predict O-GlcNAc/Phos cross talk sites based on phosphorylated sites and O-GlcNAcylated sites separately by the use of SVM model. The AUC of classifier based on phosphorylated sites is 0.896 and the other classifier based on GlcNAcylated sites is 0.843. Both classifiers achieved a relatively better performance compared with other existing methods.

Highlights

Reversible posttranslational modification (PTM) can determine a protein’s localization and activity state and interaction with other molecules by adding a modifying group or proteolytic cleavage [1]
To obtain GO terms specific to the cross talk we used human proteins having in situ O-GlcNAc/Phos sites as foreground and human proteins both phosphorylated and O-GlcNAcylated but not in the same site (O-GlcNAc + Phos) as background
Proteins with O-GlcNAc/Phos sites were significantly enriched in oxidation-reduction process (p value: 1.89E − 05), nuclear transport (p value: 2.32E − 04), and regulation of nervous system development (p value: 2.32E − 04)

Summary

Introduction

Reversible posttranslational modification (PTM) can determine a protein’s localization and activity state and interaction with other molecules by adding a modifying group or proteolytic cleavage [1]. Cross talk between posttranslational modifications can be either positive or negative [2]. Positive cross talk means one PTM can act as a signal or be recognized by a binding protein that can add or remove the other PTM while negative cross talk happens when two different kinds of PTMs compete for the same residue (in situ cross talk) or one PTM masks the recognition site of the other PTM. Further researches demonstrate that O-GlcNAc/Phos cross talk functions in signaling, chronic diseases, transcription, and cell regulation [8,9,10,11]. As only part of the exact O-GlcNAc/Phos sites

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Discussion

Conclusion