It's Got You Covered: Nf-κb in the Epidermis

Fourteen years after its initial description, the nuclear factor κB (NF-κB) signaling pathway endures as a prime example of rapidly responsive gene regulation (Sen and Baltimore 1986). Even with the complexities revealed through the elucidation of converging activation pathways and diverging downstream effectors, a generalized scheme of NF-κB signaling remains elegant in its logic: (a) external signals stimulate a kinase(s), such as NF-κB–inducing kinase (NIK), MEKK1, Akt, or TBK1/NAK, which activates the inhibitor of NF-κB protein kinase (IKK); (b) IKK then phosphorylates the inhibitor of NF-κB protein (IκB) on two critical serine residues, which targets IκB for ubiquitination and subsequent degradation by the 26S proteasome; (c) previously held captive in the cytoplasm through its association with IκB, the Rel/NF-κB dimeric transcription factor is now free to enter the nucleus, find its DNA sequence recognition motifs, and regulate...