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GW24-e3853 Identification of novel Pre-translational regulatory mechanisms for NF-kB activation
  1. Huang Xiao1,
  2. Ren Gong2,
  3. Xinyuan Li3,
  4. Fan Yang4,
  5. Irene H. Yang4,
  6. Xiao-feng Yang3,
  7. Hong Wang3,
  8. Wu Qing hua1,
  9. Xiao Shu Cheng1
  1. 1Second Affiliated Hospital of Nanchang University
  2. 2Jiangxi Provincial People’s Hospital
  3. 3Cardiovascular Research Center/Thrombosis Research Center, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140
  4. 4Department of Neurology, Yale University New Haven Hospital, New Haven, CT 06510

Abstract

Objectives NF-κB controlled transcriptional regulation plays a central role in inflammatory and immune responses. Currently understanding about NF-κB activation mechanism emphasises 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 trans-activation of NF-κB targeted genes.

Methods Pre-translational mechanism mediated NF-κB activation remains poorly understood. In this study, we investigated NF-κB pre-translational regulation by performing a series of data-base mining analysis and using six large national experimental data-bases; NCBI Unigene EST profile database, Gene Expression Omnibus (GEO) database, Transcription Element Search System (TESS) database, AceView database and Epigenomics databases, and TargetScan software.

Results We reported the following findings: 1) NF-κB signalling genes are differentially expressed in human and mouse tissues; 2) Heart and vessels are the inflammation privilege tissues and less easy to be inflamed because lacking of key NF-κB signalling molecular expression; 3) NF-κB signalling genes are induced by cardiovascular disease risk factors oxidised-phospholipids 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 signalling genes have multiple alternative promoters and alternatively spliced isoforms; 6) NF-κB family genes can be regulated by DNA methylation; 7) 27 out of 38 NF-κB signalling gene can be regulated by microRNAs.

Conclusions Our findings provide important insight into the mechanism of NF-κB activation, which may contribute to cardiovascular disease, inflammatory diseases and immunological disorders.

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