Abstract 568: Identification of Novel Pre-translational Regulatory Mechanisms for NF-?B Activation
NF-κB controlled transcriptional regulation plays a central role in inflammatory and immune responses. Currently understanding about NF-κB activation mechanism emphasizes IκB-tethered complex inactivation in the cytoplasm. In the case of NF-κB activation, IκB phosphorylation leads to its degradation followed by NF-κB relocating to the nuclear and transactivation of NF-κB targeted genes. Pre-translational mechanism mediated NF-κB activation remains poorly understood. In this study, we studied NF-κB pre-translational regulation by performed a series of data-base mining using experimental data-based NCBI Unigene EST profile database, Gene Expression Omnibus (GEO) database, Transcription Element Search System (TESS) database, AceView database, Epigenomics databases, and TargetScan software. We reported the following findings: 1) NF-κB family/signaling genes are differentially expressed in 20 human and 19 mouse tissues; 2) Heart and vessels are the inflammation privilege tissues and less easy to be inflamed because lacking of NF-κB signaling key molecular expression; 3) NF-κB activation is readily induced by cardiovascular disease risk factors oxidized-LDL and pro-inflammatory cytokines in endothelial cells; 4) Transcription factors C/EBPs and NF-κB have higher binding site frequencies in the promoters of Pro-inflammatory cytokine-induced NF-κB genes; 5) Most NF-κB signaling genes have multiple alternative promoters and alternatively spliced isoforms; 6) NF-κB family genes have DNA methylation characteristics and may be subjected to epigenetic regulation; 7) 27 out of 38 NF-κB signaling gene can be regulated by microRNAs, with the binding qualities to mRNA targets being equivalent to what have been approved experimentally. Our findings provide important insight in the mechanism of NF-κB activation, which may contribute to cardiovascular disease, inflammatory diseases and immunological disorders.
- © 2013 by American Heart Association, Inc.