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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Targeting Strategies to Modulate the NF-κB and JNK Signal Transduction Network

Author(s): Michael Kracht

Volume 6, Issue 1, 2007

Page: [71 - 84] Pages: 14

DOI: 10.2174/187152307779939705

Price: $65

Abstract

The signal transduction pathways leading to activation of Jun-NH2-terminal kinase (JNK) and nuclear factor- κB (NF-κB) are activated by a plethora of extracellular signals. Small molecules have been developed that inhibit the JNK or IκB protein kinases. Additionally, several cell-penetrating peptides have been characterized that disrupt proteinprotein interaction domains within the NF-κB and JNK signalling pathways. Usually NF-κB and JNK are (re)viewed as separate signalling systems. However, emerging evidence suggests that both pathways are interconnected at various levels. In this review, the spatiotemporal control of JNK or NF-κ B activation is discussed in conjunction with cross talk mechanisms and various regulatory feedback loops. A detailed understanding of these mechanisms is important to optimize available strategies to interfere with NF-κB or JNK signalling.

Keywords: chromatin-immunoprecipitation (ChIP), MAP kinase kinase kinases (MAKKK), ATP-competitve inhibitors, c-JUN Docking Sites, tumor necrosis factor


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