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

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.