Letter to the editor (Scientific journals)
The alternative NF-kappa B pathway from biochemistry to biology: Pitfalls and promises for future drug development
Dejardin, Emmanuel
2006In Biochemical Pharmacology, 72 (9), p. 1161-1179
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Keywords :
alternative pathway; NIK; IKK; NF-kappa B; p100/p52; inflammation
Abstract :
[en] The past two decades have led to a tremendous work on the transcription factor NF-kappa B and its molecular mechanisms of activation. The nuclear translocation of NF-kappa B is controlled by two main pathways: the classical and the alternative NF-kappa B pathways. The classical NF-kappa B pathway activates the IKK complex that controls the inducible degradation Of Most I kappa B family members that are I kappa B alpha, I kappa B beta, I kappa B epsilon and p105. The alternative NF-kappa B pathway induces p100 processing and p52 generation through the activation of at least two kinases, which are NIK and IKK alpha. Genetic studies have shown that IKK gamma is dispensable for the alternative pathway, which suggests the existence of an alternative IKK alpha-containing complex. It is noteworthy that activation of particular p52 heterodimers like p52/RelB requires solely the alternative pathway while activation of p52/p65 or p52/c-Rel involves a "hybrid pathway". Among others, LT beta R, BAFF-R, CD40 and RANK have the ability to induce the alternative pathway. The latter plays some roles in biological functions controlled by these receptors, which are the development of secondary lymphoid organs, the proliferation, survival and maturation of B cell, and the osteoclastogenesis. Exacerbated activation of the alternative pathway is potentially associated to a wide range of disorders like rheumatoid arthritis, ulcerative colitis or B cell lymphomas. Therefore, inhibitors of the alternative pathway could be valuable tools for the treatment of inflammatory disorders and cancers. (c) 2006 Elsevier Inc. All rights reserved.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Dejardin, Emmanuel ;  Université de Liège - ULiège > Virologie - Immunologie
Language :
English
Title :
The alternative NF-kappa B pathway from biochemistry to biology: Pitfalls and promises for future drug development
Publication date :
30 October 2006
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Pergamon-Elsevier Science Ltd, Oxford, United Kingdom
Volume :
72
Issue :
9
Pages :
1161-1179
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 14 November 2011

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