High plasma levels of VLDL are associated with increased risk for atherosclerosis. Here we show that VLDL (75 to 150 mg/mL) activates nuclear factor-kB (NF-kB), a transcription factor known to play a key role in regulation of inflammation. Oxidation of VLDL reduced its capacity to activate NF-kB in vitro, whereas free fatty acids such as linoleic and oleic acid activated NF-kB to the same exten...

A central mediator of a wide host of target genes, the nuclear factor-KB (NF-KB) family of transcription factors, has emerged as a molecular target in cancer and diseases associated with bone destruction. To evaluate how NF-KB signaling in tumor cells regulates processes associated with osteolytic bone tumor burden, we stably infected the boneseeking MDA-MB-231 breast cancer cell line with a do...

D ow lo Glioblastoma multiforme (GBM) is the most common and lethal form of intracranial tumor. We have established a lentivirus-induced mouse model of malignant gliomas, which faithfully captures the pathophysiology and molecular signature of mesenchymal human GBM. RNA-Seq analysis of these tumors revealed high nuclear factor kB (NF-kB) activation showing enrichment of known NF-kB target genes...

main of approximately 100 amino acids in length. All IkBa regulates the transcription factor NF-kB through dimerization contacts are mediated through this second the formation of stable IkBa/NF-kB complexes. Prior domain, referred to as the dimerization domain. The to induction, IkBa retains NF-kB in the cytoplasm until carboxy-terminal 13 amino acids (NLS polypeptide), the the NF-kB activation...

NF-kB refers to multiple dimers of Rel homology domain (RHD) containing polypeptides, which are controlled bya stimulus-responsive signaling system that mediates the physiological responses to inflammatory intercellular cytokines, pathogen exposure, and developmental signals. TheNF-kBsignalingsystemoperatesontransientor short timescales, relevant to inflammation and immune responses, and on lon...

Activation of NF-kB following genotoxic stress allows time for DNA-damage repair and ensures cell survival accounting for acquired chemoresistance, an impediment to effective cancer therapy. Despite this clinical relevance, little is known about pathways that enable genotoxic-stress-induced NF-kB induction. Previously, we reported a role for the p53-inducible death-domaincontaining protein, PID...

Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2-positive breast cancer, but resistance inevitably occurs. We previously found that NF-kB is hyperactivated in a subset of HER2-positive breast cancer cells and tissue specimens. In this study, we report that constitutively active...

Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-de...

Objective—Chlamydia pneumoniae has been associated with atherosclerosis. Infection of vascular endothelial cells with C pneumoniae increases the expression of proatherogenic cytokines mediated by nuclear factor (NF)-kB, a transcription factor. The present study was designed to test the effect of aspirin on C pneumoniae–induced NF-kB activation, interleukin expression, and bacterial development ...

TNF receptor 1 (TNFR1) can trigger opposing responses within the same cell: a prosurvival response or a cell-death pathway [1, 2]. Cell survival requires NF-kB-mediated transcription of prosurvival genes [3–9]; apoptosis occurs if NF-kB signaling is blocked [5, 7–9]. Hence, activation of NF-kB acts as a cell-death switch during TNF signaling. This study demonstrates that the pathway includes an...