NF-kB essential modulator (NEMO), the regulatory subunit of the IkB kinase (IKK) that activates NF-kB, is essential for NF-kB activation [1]. NEMO was recently found to contain a region that preferentially binds Lys (K)63-linked but not K48-linked polyubiquitin (polyUb) chains, and the ability of NEMO to bind to K63-linked polyUb RIP (receptor-interacting protein) is necessary for efficient tum...

The IKK kinase complex is the core element of the NF-kB cascade. It is essentially made of two kinases (IKKa and IKKb) and a regulatory subunit, NEMO/IKKg. Additional components may exist, transiently or permanently, but their characterization is still unsure. In addition, it has been shown that two separate NF-kB pathways exist, depending on the activating signal and the cell type, the canonic...

The transcription factor, nuclear factor kappa B (NF-kB) is one of the principal inducible protein in mammals known to control the gene expression in many critical physiological responses such as oxidative stress, inflammation etc. and has been shown to play an important role in the pathogenesis of cancer. Terpenoids are major constituents present in nutritionally used fruits, vegetables and di...

Classic studies over the last two decades have made virus-induced activation of the mammalian interferon-b (ifnb) gene a prototype of eukaryotic gene regulation [1–6]. Indeed, the compact ,50 base-pair enhancer region upstream of the ifnb transcription start site is amongst the beststudied stretches of mammalian DNA, and its function in regulation of ifnb expression is considered a paradigm of ...

active protein (CRP) is a prototypic marker of inflammation, and has been shown in numerous prospective studies to predict cardiovascular events. CRP is both a risk marker and evolved to promote atherogenesis. To date, it has been shown that in endothelial cells, CRP increases the expression of cell adhesion molecules, monocyte-chemotactic protein-1, endothelin-1 and plasminogen activator inhib...

The chemokine stromal-derived factor-1A (SDF-1A/CXCL-12) and its receptor, CXCR4, play a crucial role in adhesion and transendothelium migration (TEM) of prostate cancer cells. We tested the hypothesis that enhanced expression of CXCR4 in prostate cancer cells is dependent upon SDF-1A-mediated activation of nuclear factor-KB (NF-KB). SDF-1A increased the CXCR4 mRNA and protein expression in PC-...

One mechanism leading to neurodegeneration during Alzheimer’s disease (AD) is amyloid b peptide (Ab) neurotoxicity. Ab elicits in cultured central nervous system neurons a biphasic response: a low-dose neurotrophic response and a high-dose neurotoxic response. Previously we reported that NF-kB is activated by low doses of Ab only. Here we show that NF-kB activation leads to neuroprotection. In ...

Background: Experimental models of cancer cachexia have indicated that systemic inflammation induces muscle-protein breakdown and wasting via muscular nuclear transcription factor kB (NF-kB) activation. This process may limit the efficacy of nutritional intervention. Objectives: We assessed muscle NF-kB activity and protein turnover signaling in progressive stages of clinical lung cancer cachex...

tor–associated factor (TRAF) family of adaptor proteins Activation of the transcription factor NF-kB by tumor as signal transducers (Rothe et al., 1995a; Cao et al., necrosis factor (TNF) and interleukin-1 (IL-1) requires 1996a; Hsu et al., 1996a). TRAF proteins associate dithe NF-kB-inducing kinase (NIK). In a yeast two-hybrid rectly with the cytoplasmic domain of several members screen for NI...

Inflammation is linked clinically and epidemiologically to cancer, and NF-kB appears to play a causative role, but the mechanisms are poorly understood. We show that transient activation of Src oncoprotein can mediate an epigenetic switch from immortalized breast cells to a stably transformed line that forms self-renewing mammospheres that contain cancer stem cells. Src activation triggers an i...