The molecular mechanisms associated with PIN7, a protein-protein interaction network of seven pleiotropic proteins
- Published
- Accepted
- Subject Areas
- Biochemistry, Bioinformatics, Molecular Biology, Data Mining and Machine Learning, Data Science
- Keywords
- protein-protein interaction networks, Warburg effect, TPPII, CDK2, SIRT6, SIRT7, BSG, PTK2 signaling, aging, p53 signaling
- Copyright
- © 2019 Nahálková
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2019. The molecular mechanisms associated with PIN7, a protein-protein interaction network of seven pleiotropic proteins. PeerJ Preprints 7:e27547v1 https://doi.org/10.7287/peerj.preprints.27547v1
Abstract
The protein-protein interaction network of seven pleiotropic proteins (PIN7) contains proteins with multiple functions in the aging and age-related diseases (TPPII, CDK2, MYBBP1A, p53, SIRT6, SIRT7, and BSG). At the present work, the pathway enrichment, the gene function prediction and the protein node prioritization analysis were applied for the examination of main molecular mechanisms driving PIN7 and the extended network. Seven proteins of PIN7 were used as an input for the analysis by GeneMania, a Cytoscape application, which constructs the protein interaction network. The software also extends it using the interactions retrieved from databases of experimental and predicted protein-protein and genetic interactions. The analysis identified the p53 signaling pathway as the most dominant mediator of PIN7. The extended PIN7 was also analyzed by Cytohubba application, which showed that the top-ranked protein nodes belong to the group of histone acetyltransferases and histone deacetylases. These enzymes are involved in the reverse epigenetic regulation mechanisms linked to the regulation of PTK2, NFκB, and p53 signaling interaction subnetworks of the extended PIN7. The analysis emphasized the role of PTK2 signaling, which functions upstream of the p53 signaling pathway and its interaction network includes all members of the sirtuin family. Further, the analysis suggested the involvement of molecular mechanisms related to metastatic cancer (prostate cancer, small cell lung cancer), hemostasis, the regulation of the thyroid hormones and the cell cycle G1/S checkpoint. The additional data-mining analysis showed that the small protein interaction network MYBBP1A-p53-TPPII-SIRT6-CD147 controls Warburg effect and MYBBP1A-p53-TPPII-SIRT7-BSG influences mTOR signaling and autophagy. Further investigations of the detail mechanisms of these interaction networks would be beneficial for the development of novel treatments for aging and age-related diseases.
Author Comment
The manuscript represents the final version, and it is not submitted for review anywhere else.
