The NF-κB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IκB-α protein. In response to many different NF-κB-inducing agentsincluding T-cell mitogens, proinflammatory cytokines, and viral transactivatorsthe inhibitory IκB-α is rapidly phosphorylated and degraded. Phosphorylation of IκB-α at Ser32 and Ser36 has been shown to stimulate conjugation with ubiquitin and subsequent degradation of IκB-α. Phosphorylation of IκB-α at Ser32 and Ser36 is critical for activation of NF-κB, which then translocates to the nucleus and induces transcription of genes that protect organism.
