Signaling Interface of Advanced Glycation Endproducts Receptor and Ubiquitin-Conjugating Enzyme Ubc9 Complex in Atherosclerosis and Cancer Cells

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SURMylation-mediated cellular pathways. Previous studies have shown that both the AGE-R and Ubc9 play a role in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between the AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.