Targeting Strategies to Modulate the NF-&kgr;B and JNK Signal Transduction Network

Publisher: Bentham Science Publishers

E-ISSN: 1875-614x|6|1|71-84

ISSN: 1871-5230

Source: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents), Vol.6, Iss.1, 2007-02, pp. : 71-84

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Abstract

The signal transduction pathways leading to activation of Jun-NH2-terminal kinase (JNK) and nuclear factor- &kgr;B (NF-&kgr;B) are activated by a plethora of extracellular signals. Small molecules have been developed that inhibit the JNK or I&kgr;B protein kinases. Additionally, several cell-penetrating peptides have been characterized that disrupt proteinprotein interaction domains within the NF-&kgr;B and JNK signalling pathways. Usually NF-&kgr;B 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-&kgr; 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-&kgr;B or JNK signalling.