The nuclear factor kappa B (NFkB) is a ubiquitous transcription factor essential for the activation of immune and inflammatory responses. NFkB activity is inhibited when it is associated with IkB proteins in the cell cytoplasm. IkB proteins are phosphorylated by the IkB kinase complex. The IKK serine protein kinase consists of alpha and beta subunits (IKK alpha and IKK beta). These subunits interact with each other and together, are essential for NFkB activation. IKK alpha is expressed in variety of human tissues. The targeted disruption of the IKK alpha gene in mice results in severe skin and limb abnormalities and newborn death. USCD researchers used an IKK alpha antibody to identify specific protein functions dependent on catalytic activity1. They determined that during mammary gland development, IKK alpha is an essential link connecting RANK and cyclin D1 expression. The IKK alpha antibody was also used to study the role of the proinflammatory cytokine IL-18 on both intrinsic and extrinsic apoptotic signaling mechanisms in endothelial cells2. Based on their studies, it appears that IL-18 induces endothelial cell death and may be involved in myocardial injury and inflammation.
An Austrian group published a tandem affinity purification (TAP) method in Nature Methods that relied upon a IKK alpha antibody to purify protein complexes from lesser amounts of starting material, thus allowing greater success in and more systematic proteomics projects3. This novel protocol was validated on the Ku70-Ku80 complex to demonstrate the identification of the expected core elements but also new candidate effectors. Eckmann et al used the IKK alpha antibody in their murine model studies on IKK inhibitors to minimize and repair acute and chronic intestinal inflammation due to cell loss and ulceration4. Data from Alameda’s group in non-melanoma skin cancers suggests that elevated IKK alpha levels increase skin tumor malignancy potential. Those researchers generated expression profiles with the aid of a IKK alpha antibody5 as well.
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