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

The advanced glycation endproducts receptor (AGE-R) has been established as a signal transduction receptor for multiligand such as S100b and AGEs. These molecules have been demonstrated to activate various cells with important links to atherosclerosis initiation and progression including endothelial cells and smooth muscle cells via AGER, triggering activation of multiple signaling cascades through its cytoplasmic domain. Very Recently, Small Ubiquitin-Related Modifier 1 (SURM-1 also known as SUMO-1) has recently been recognized as a protein that plays a diverse role in cellular post-translational modifications. SURM-1 functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin, which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, apoptosis, and protein stability. Computer Database search indicated that AGE-R has the conserved consensus SURMylation motif, defined as yKXE. The five potential SURMylation sites wereidentified in human AGE-R. The presence of the consensus yKXE motif in the AGE-R strongly suggests that AGE-R may be regulated by SURMylation process. Our results suggest that AGE-R is SURMylated in a living vascular and other cell system. Fully utilizing the power of complementary bioinformatics and molecular biological approaches, we determined the interactions of AGE-R and SURM-1 in a living vascular 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.