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The Bioinformatics and Molecular Biology Approaches for Vascular Cell Signaling by Advanced Glycation Endproducts Receptor and Small Ubiquitin-Related Modifier

  • Kim, June Hyun (Department of Bioscience and Biotechnology, The University of Suwon)
  • Received : 2012.09.27
  • Accepted : 2012.10.11
  • Published : 2012.12.31

Abstract

The advanced glycation endproducts receptor (AGE-R) is a signal transduction receptor for multiligand such as S100b and AGEs. S100b has been demonstrated to activate various cells with important links to atherosclerosis initiation and progression including endothelial cells, and smooth muscle cells via AGE-R, triggering activation of multiple signaling cascades through its cytoplasmic domain. Many studies have suggested AGE-R might even participate in the cardiovascular complications involved in the pathogenesis of type I diabetes. Recently, Small Ubiquitin-Related Modifier 1 (SURM-1 also known as SUMO-1) has been recognized as a protein that plays an important role in cellular post-translational modifications in a variety of cellular processes, such as transport, transcriptional, apoptosis and stability. Computer Database search with SUMOplot Analysis program identified the five potential SURMylation sites in human AGE-R: K43, K44, K123, and K273 reside within the extracellular domain of AGE-R, and lastly K374 resides with the cytosolic domain of AGE-R. The presence of the consensus yKXE motif in the AGE-R strongly suggests that AGE-R may be regulated by SURMylation process. To test this, we decided to determine if AGE-R is SURMylated in living vascular cell system. S100b-stimulated murine aortic vascular smooth muscle cells were used for western blot analysis with relevant antibodies. Taken together, bioinformatics database search and molecular biological approaches suggested AGE-R is SURMylated in living cardiovascular cell system. Whilst SURMylation and AGE-R undoubtedly plays an important role in the cardiovascular biology, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

Keywords

References

  1. Brune, M., Muller, M., Melino, G., Bierhaus, A., Schilling, T., and Nawroth, P. P. (2012). Depletion of the receptor for advanced glycation end products (RAGE) sensitizes towards apoptosis via p53 and p73 posttranslational regulation. Oncogene.
  2. Kim, W., Hudson, B. I., Moser, B., Guo, J., Rong, L. L., Lu, Y., Qu, W., Lalla, E., Lerner, S., Chen, Y., et al. (2005). Receptor for advanced glycation end products and its ligands: a journey from the complications of diabetes to its pathogenesis. Ann N Y Acad Sci 1043, 553-561. https://doi.org/10.1196/annals.1338.063
  3. Yan, S. F., Ramasamy, R., and Schmidt, A. M. (2010). The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res 106, 842-853. https://doi.org/10.1161/CIRCRESAHA.109.212217
  4. Praefcke, G. J., Hofmann, K., and Dohmen, R. J. (2012). SUMO playing tag with ubiquitin. Trends Biochem Sci 37, 23-31. https://doi.org/10.1016/j.tibs.2011.09.002
  5. Zungu, M., Schisler, J., and Willis, M. S. (2011). All the little pieces. -Regulation of mitochondrial fusion and fission by ubiquitin and small ubiquitin-like modifer and their potential relevance in the heart. Circ J 75, 2513-2521. https://doi.org/10.1253/circj.CJ-11-0967
  6. Watanabe, M., and Itoh, K. (2011). Characterization of a novel posttranslational modification in neuronal nitric oxide synthase by small ubiquitin-related modifier-1. Biochim Biophys Acta 1814, 900-907. https://doi.org/10.1016/j.bbapap.2011.04.006
  7. Xue, Y., Zhou, F., Fu, C., Xu, Y., and Yao, X. (2006). SUMOsp: a web server for sumoylation site prediction. Nucleic Acids Res 34, W254-257. https://doi.org/10.1093/nar/gkl207
  8. Ren, J., Gao, X., Jin, C., Zhu, M., Wang, X., Shaw, A., Wen, L., Yao, X., and Xue, Y. (2009). Systematic study of protein sumoylation: Development of a site-specific predictor of SUMOsp 2.0. Proteomics 9, 3409- 3412. https://doi.org/10.1002/pmic.200800646
  9. Xu, J., He, Y., Qiang, B., Yuan, J., Peng, X., and Pan, X. M. (2008). A novel method for high accuracy sumoylation site prediction from protein sequences. BMC Bioinformatics 9, 8. https://doi.org/10.1186/1471-2105-9-8
  10. Zhou, F., Xue, Y., Lu, H., Chen, G., and Yao, X. (2005). A genome-wide analysis of sumoylation-related biological processes and functions in human nucleus. FEBS Lett 579, 3369-3375. https://doi.org/10.1016/j.febslet.2005.04.076
  11. Liu, B., Li, S., Wang, Y., Lu, L., Li, Y., and Cai, Y. (2007). Predicting the protein SUMO modification sites based on Properties Sequential Forward Selection (PSFS). Biochem Biophys Res Commun 358, 136-139. https://doi.org/10.1016/j.bbrc.2007.04.097
  12. Kim, W. J., Chereshnev, I., Gazdoiu, M., Fallon, J. T., Rollins, B. J., and Taubman, M. B. (2003). MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury. Biochem Biophys Res Commun 310, 936-942. https://doi.org/10.1016/j.bbrc.2003.09.088