Article

Linking JNK signaling to NF-κB: a key to survival

The Ben May Institute for Cancer Research, The University of Chicago, 924 East 57th Street, Chicago, IL 60637, USA.
Journal of Cell Science (Impact Factor: 5.43). 11/2004; 117(Pt 22):5197-208. DOI: 10.1242/jcs.01483
Source: PubMed

ABSTRACT

In addition to marshalling immune and inflammatory responses, transcription factors of the NF-kappaB family control cell survival. This control is crucial to a wide range of biological processes, including B and T lymphopoiesis, adaptive immunity, oncogenesis and cancer chemoresistance. During an inflammatory response, NF-kappaB activation antagonizes apoptosis induced by tumor necrosis factor (TNF)-alpha, a protective activity that involves suppression of the Jun N-terminal kinase (JNK) cascade. This suppression can involve upregulation of the Gadd45-family member Gadd45beta/Myd118, which associates with the JNK kinase MKK7/JNKK2 and blocks its catalytic activity. Upregulation of XIAP, A20 and blockers of reactive oxygen species (ROS) appear to be important additional means by which NF-kappaB blunts JNK signaling. These recent findings might open up entirely new avenues for therapeutic intervention in chronic inflammatory diseases and certain cancers; indeed, the Gadd45beta-MKK7 interaction might be a key target for such intervention.

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Available from: Francesca Zazzeroni, Sep 25, 2015
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    • "NF-κB activation in response to TNFR1 engagement promotes termination of JNK activation through a mechanism that depends on the induction of antioxidant enzymes such as manganese superoxide dismutase (MnSOD) and ferritin heavy chain (FHC), as reactive oxygen species (ROS) help to sustain JNK activity (Kamata et al. 2005; Pham et al. 2004). In addition, interference with JNK activity can be achieved through NF-κB-dependent upregulation of genes encoding inhibitors of JNK signaling such as GADD45β, XIAP, and A20 (De Smaele et al. 2001; Papa et al. 2004; Tang et al. 2001). In many cell types, suppression of JNK-induced apoptosis can contribute to the tumor-promoting activities of NF-κB (Nakano et al. 2006; Papa et al. 2006). "

    Full-text · Article · Feb 2015
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    • "NF-κB activation in response to TNFR1 engagement promotes termination of JNK activation through a mechanism that depends on the induction of antioxidant enzymes such as manganese superoxide dismutase (MnSOD) and ferritin heavy chain (FHC), as reactive oxygen species (ROS) help to sustain JNK activity (Kamata et al. 2005; Pham et al. 2004). In addition, interference with JNK activity can be achieved through NF-κB-dependent upregulation of genes encoding inhibitors of JNK signaling such as GADD45β, XIAP, and A20 (De Smaele et al. 2001; Papa et al. 2004; Tang et al. 2001). In many cell types, suppression of JNK-induced apoptosis can contribute to the tumor-promoting activities of NF-κB (Nakano et al. 2006; Papa et al. 2006). "
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    • "It is also known that targeting IKK also may affect other pathways in addition to NF-кB. For example, IKK affects p53, FOXO3A, and HIF-1 in addition to NF-кB [22, 23]. "
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