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
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Title: Targeting Strategies to Modulate the NF-κB and JNK Signal Transduction Network
Volume: 6 Issue: 1
Author(s): Michael Kracht
Affiliation:
Keywords: chromatin-immunoprecipitation (ChIP), MAP kinase kinase kinases (MAKKK), ATP-competitve inhibitors, c-JUN Docking Sites, tumor necrosis factor
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.
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Cite this article as:
Kracht Michael, Targeting Strategies to Modulate the NF-κB and JNK Signal Transduction Network, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2007; 6 (1) . https://dx.doi.org/10.2174/187152307779939705
DOI https://dx.doi.org/10.2174/187152307779939705 |
Print ISSN 1871-5230 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-614X |
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