Editors' ChoiceDifferentiation

New Functions for IKKα

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Science's STKE  10 Apr 2001:
Vol. 2001, Issue 77, pp. tw2
DOI: 10.1126/stke.2001.77.tw2

IKKα is a protein kinase best known and named for its participation in the activation of the transcription factor NF-κB as a subunit of the inhibitor of κB (IκB) kinase (IKK). IKKα activity can be replaced by protein kinase IKKβ in IKK for the purposes of activation of the NF-κB pathway. Mice in which the IKKα gene has been disrupted (Ikkα-/-) show defects in epidermal differentiation. However, primary keratinocyte cultures from these mice exhibit enhanced NF-κB activity in response to activators of this pathway such as tumor necrosis factor-α or interleukin-1, suggesting that the differentiation defect is not the result of impaired NF-κB signaling. By transfecting cultured keratinocytes with various IKKα mutants and monitoring differentiation potential, Hu et al. showed that the IKKα kinase activity is dispensible for restoring normal differentiation to the Ikkα-/- cells; however, the NH2 terminus, the helix-loop-helix domain, and the leucine zipper were important for inducing differentiation. Ikkα-/- keratinocytes transplanted into normal mice differentiated normally, suggesting that the Ikkα-/- cells lacked a secreted differentiation factor. Analysis of conditioned medium from cultured wild-type and Ikkα-/- cells demonstrated the lack of a soluble factor in the medium of the mutant cells, which Hu et al. have named keratinocyte differentiation-inducing factor (kDIF). Thus, IKKα participates in the transcriptional regulation of kDIF in a manner that is independent of its function in IκB kinase and NF-κB activation.

Y. Hu, V. Baud, T. Oga, K. I. Kim, K. Yoshida, M. Karin, IKKα controls formation of the epidermis independently of NF-κB. Nature 410, 710-714 (2001). [Online Journal]

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