IκBα (cleavage specific)

The NF-κB/Rel transcription factors are present in the cytosol in an inactive state complexed with the inhibitory IκB proteins. Activation of IκBα occurs through both serine and tyrosine phosphorylation events. Activation through phosphorylation at Ser-32 and Ser-36 is followed by proteasome-mediated degradation, resulting in the release and nuclear translocation of active NF-κB. This pathway of IκBα regulation occurs in response to various NF-κB-activating agents, such as TNFα, interleukins, LPS, and irradiation. Alternatively, Tyr-42 phosphorylation in response to oxidative stress and growth factors leads to degradation of IκBα and increased NF-κB-activation. In contrast, Tyr-305 phosphorylation by c-Abl has been implicated in IκBα nuclear translocation and inhibition of NF-κB-activation. In addition, IκBα can be cleaved by caspases during apoptosis to produce an amino-terminal truncated IκBα (DN-IκBα). The DN-IκBα is resistant to degradation in response to inducers of NF-κB and acts as a dominant inhibitory molecule that suppresses NF-κB activity during apoptosis.

References