Nuclear factor kappa B (NFκB) is a dimeric transcription factor comprised of five family members RelA (p65), RelB, c-Rel, p50 and p52. NFκB signalling is complex and controls a myriad of normal cellular functions. However, constitutive or aberrant activation of this pathway is associated with disease progression and cancer in multiple organs. The diverse array of biological responses is modulated by many factors, including the activating stimulus, recruitment of co-regulatory molecules, consensus DNA binding sequence, dimer composition and post-translational modifications. Each subunit has very different biological functions and in the context of disease the individual subunits forming the NFκB dimer can have a profound effect, causing a shift in the balance from normal to pathogenic signalling. Here we discuss the role of c-Rel dependant signalling in normal physiology and its contribution to disease both inside and outside of the immune system.
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