Linking TPP2 to the protein interaction and signalling networks

The present manuscript explores signalling and metabolic pathways which mediate functions of Tripeptidyl-peptidase 2 (TPP2) using the analysis of its protein-protein interaction network. The protein interaction data were retrieved partially from our previous experimental published work and the public databases. The interacting proteins were collected from BioGRID 3.5.169; STRING and Agilent Literature Search 3.1.1 databases based on the increased threshold criteria. Totally 13 interacting proteins were obtained from the public sources, and they were combined with TPP2 interacting proteins included in the interaction network PIN7, which involves seven interacting proteins with the pleiotropic functions involved in tumorigenesis, neurodegeneration and ageing. The interaction network of TPP2 was analysed by the pathway enrichment, the protein function prediction and the protein node prioritisation analysis by GeneMania and Cytohubba applications run under Cytoscape 3.7.0 environment. The most enriched signalling pathways were functionally linked to the regulation of the adaptive and innate immunity (ID, Kit Receptor, BCR, IL2, the regulation of NFκB), the aerobic glycolysis (ID and IL-2), tumorigenesis (TGF β, p53, the high priority nodes MAPKs, and the control of mTOR), diabetes (Kit receptor, the top priority node GSK3 β ) and neurodegeneration (the regulation of mTOR and A β peptide degradation). The BioGRID database mining also showed the interaction with two lung cancer suppressors (DOK3, DENND2D), a protein involved in the increased risk of the lung cancer in smokers (CYP1A1) and a protein involved in asthmatic reactions (CHIA). The potentially unexplored functions of TPP2 in the lung pathologies are also discussed with regards to these interactions. Additional interesting functions might suggest the interaction with methyltransferase CARNMT1, which modifying di- and tripeptides and the xenobiotic processing enzyme CYP1A1.