Life (and Death) Without NEMO

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Science  30 Jun 2000:
Vol. 288, Issue 5475, pp. 2285
DOI: 10.1126/science.288.5475.2285b

The NF-κB signaling pathway has captured general attention because of its prominent role in cell survival and proliferation, immune and stress responses, and inflammatory reactions. Adding to interest in this pathway is the discovery that inherited genetic alterations in one of its key regulatory components are responsible for an X-linked human disease called incontinentia pigmenti (IP). Males with IP usually die before birth, whereas heterozygous females display variable abnormalities of the skin, hair, nails, central nervous system, and other tissues.

Smahi et al. show that most patients with IP have mutations in the gene encoding NF-κB essential modulator (NEMO), a protein required for activation of the NF-κB transcription factor. In parallel studies, Makris et al. and Schmidt-Supprian et al. show that female mice heterozygous for NEMO deficiency develop skin lesions and other characteristic features of human IP. Signaling via NF-κB can prevent cell death, leading the authors to speculate that loss of NF-κB activation by NEMO contributes to the embryonic lethality in males and to the selective loss of NEMO-deficient cells seen in females. – PAK

Nature405, 466 (2000); Mol. Cell5, 969 (2000); Mol Cell5, 981 (2000).

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