RelA/NF-kB - A proinflammatory signaling pathway with roles in immunity and cancer

Mon, 12/21/2015 - 14:49

The inflammatory response consists of a complex network of signaling pathways that regulate a diverse set of cytokines, growth factors, adhesion molecules, and transcription factors (1). Of the proinflammatory signaling pathways the NF-kB family is particularly well studied for its role in apoptosis, cancer, and the development and maintenance of the immune system (1). The family consists of the transcription factors p50, p52, RelA (p65), RelB, and c-Rel. Each of these share the Rel homology domain (RHD) that is responsible for dimerization and DNA binding (2). Under normal conditions NF-kB exists as a cytoplasmic dimer in an inactive state associated with the IkB proteins (2). Stimuli, such as a microbial infection, activate TNF receptor or Toll-like receptors to activate the IkB kinase complex leading to the ubiquitination and degradation of IkB proteins (2).  This releases NF-kB and allows translocation to the nucleus and activation of target genes (2). In addition to extracellular signals, NF-kB can be activated in response to intracellular stress such as DNA damage, reactive oxygen species, or intracellular pathogens (2). NF-kB is implicated in a variety of inflammatory disorders including asthma, Crohn’s disease, and rheumatoid arthritis (1). As such NF-kB has been considered a target for the development of anti-inflammatory drugs (2). In addition, observed mutations or constitutive activation of NF-kB in various cancers has shed light on the interplay between inflammatory pathways and tumorigenesis (3). The ability to monitor NF-kB expression levels and activity using NF-kB antibodies facilitates research with applications in a variety of disease areas.

Following nuclear translocation of NF-kB is a convenient way to monitor the inflammatory response through either cell fractionation followed by western blotting or through immunhistochemistry. Das et al. demonstrated both of these techniques using NF-kB antibodies in their examination of inflammation induced by ionizing radiation (4). Similarly, Rasheed et al. from the University of South Carolina used an NF-kB antibody to in their characterization of a natural product derived from green tea with potential for treating osteoarthritis (5). In their study drug treatment prevent nuclear accumulation of NF-kB presumably through the inhibition of the IKK complex (5). Analysis of macrophage differentiation by Chang et al. revealed a novel mechanism of NF-kB regulation through lysosomal degradation (6). Immunofluorescence experiments with an NF-kB antibody demonstrated selective autophagy of NF-kB protein (6). This study showed NF-kB protein degradation is mediated by the autophagy receptor p62/SQSTM1 (6). Inflammation plays a central role in a variety of human diseases making NF-kB a key target for further research. NF-kB antibodies provide a valuable tool for this research and will facilitate drug development studies and provide insight into complex inflammatory responses.

Novus Biologicals offers RelA/NFkB p65 reagents for your research needs including:


  1. 20457564
  2. 22302935
  3. 23915189
  4. 24854039
  5. 19445683
  6. 23175187

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