Phospho-IκBα / NFκB Translocation
phosphorylation of IκBα leads to the activation of NFκB
NFκB proteins are among the most widely studied transcription factors because they have been shown to regulate a variety of genes that control inflammation, cell proliferation and cell survival. In addition, aberrant activity of NFκB has been observed in many human cancers.
In unstimulated cells, NFκB dimers are sequestered in an inactive state in the cytoplasm by the IκB family of inhibitor proteins, which mask the nuclear localization signals of the NFκB proteins. The best-studied IκB protein is IκBα. In response to a variety of external stimuli, human IκBα is phosphorylated at Ser32 & Ser36 by IκB Kinase (IKK) proteins. This results in the ubiquitination, dissociation from NFκB and degradation of IκBα. The newly "freed" NFκB complex can then translocate to the nucleus where it regulates gene expression through DNA binding (see Diagram below).