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Cytokine Growth Factor Rev. 2006 Aug;17(4):281-93. Epub 2006 Jun 21.

Alternative pathways of NF-kappaB activation: a double-edged sword in health and disease.

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  • 1Department of Cell Biology and Neuroscience, W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.


While the classical pathway of NF-kappaB activation plays critical roles in a wide range of biological processes, the more recently described "non-canonical" NF-kappaB pathway has important but more restricted roles in both normal and pathological processes. The non-canonical NF-kappaB pathway, based on processing of the nf-kappab2 gene product p100 to generate p52, appears to be involved in B-cell maturation and lymphoid development. Deregulated activation of this pathway has been observed in a variety of malignant and autoimmune diseases, thus inhibitors that specifically target p100 processing might be predicted to have potential roles as immunomodulators and in the therapy of malignant diseases. We review current understandings of NF-kappaB activation, particularly the mechanisms of p100 processing under both physiological and pathological conditions.

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