NFkB is a transcription factor involved in the regulation of genes encoding mediators of the immune, acute phase and inflammatory responses. The transcription factor binds to a specific DNA sequence (5´ – GGGACTTTCC – 3´) in the promoter region of these genes. The protein complex which makes up NFkB is composed of Rel family homo and heterodimeric subunits: p50, p65 (RelA), c-Rel, p52 and RelB. These proteins all have a 300 amino acid long sequence in common in the N-terminal region – the N Rel homology domain. It is this domain that regulated DNA binding, nuclear localization and dimerization, and it is this domain that is targeted by IkB inhibitors such as IkBα, IkBβ, IkBγ, Bcl-3, p105 and p100. Different dimer combinations of the NFkB subunits have distinctive DNA sequence binding specificities, activating different categories of genes including cytokines immunoreceptors and adhesion molecules.
In most cells, NFkB remains bound to the IkB proteins, maintained in an inactive form. When cells are treated with various inducers (such as lipopolysaccharide, or inflammatory cytokines, such as TNF-α or IL-1β), however, the IkB proteins undergo phosphorylation, ubiquitination and degradation. Proteolytic cleavage of p105 generates two proteins – p50, which, though it binds to DNA, has no transactivation domain, and its antagonist, the inhibitor IkBy protein. The release of the NFkB dimers, and their translocation to the nucleus and activation of their target genes follows.
For those researchers seeking to study this fascinating signaling pathway, and its relation to various biological processes including but not limited to cancer, securing all regulatory components in the pathway from the same source, at a high and uniform quality is a must to achieve dependable results.
Merkel is happy to provide exactly that – as well as technical advice and assistance in making the most out of your purchase.