NF-κB's Arsenal to Blunt JNK

Science's STKE  20 Nov 2001:
Vol. 2001, Issue 109, pp. tw423
DOI: 10.1126/stke.2001.109.tw423

The paradox of the cytokine tumor necrosis factor-α (TNF-α) is that it can induce both cell survival and cell death in immune and nonimmune cells. Activation of the TNF receptor stimulates both the prosurvival nuclear factor-kappa B (NF-κB) signaling cascade and the proapoptotic c-Jun amino terminal kinase (JNK) pathway. Two reports indicate that these pathways communicate with each other to regulate a cell's ultimate fate. De Smaele et al. found that the transcription factor NF-κB induces the expression of a protein called Gadd45β, which acts as a negative regulator of JNK. Inhibiting Gadd45β expression resulted in sustained JNK activity. Gadd45β had no effect on the MAP kinases ERK and p38. Tang et al. show that X-chromosome-linked inhibitor of apoptosis (XIAP), a known target of NF-κB, also attenuated JNK activity. The mechanisms by which these two target proteins of NF-κB inhibit JNK have yet to be defined. It will also be of interest to determine how the TNF receptor favors the activation of one pathway or the other to possibly influence the cross talk.

E. De Smaele, F. Zazzeroni, S. Papa, D.U. Nguyen, R. Jin, J. Jones, R. Cong, G. Franzoso, Induction of Gadd45β by NF-κB donwregulates pro-apoptotic JNK signalling. Nature 414, 308-313 (2001). [Online Journal]

G. Tang, Y. Minemoto, B. Dibling, N.H. Purcell, Z. Li, M. Karin, A. Lin, Inhibition of JNK activation through NF-κB target genes. Nature 414, 313-317 (2001). [Online Journal]