JNK: a killer on a transcriptional leash.

Abstract

Whether to live or die is arguably the most important decision a cell has to make, and the NF-B/Rel group of transcription factors is a key element in this decision. Since the discovery of the Anti-Apoptotic Function of NF-B in 1996, the number of publications dealing with the control of apoptosis by NF-B has increased at an astonishing pace – over 600 papers were published in the last 18 months alone! This plethora of publications underscores the crucial role that this particular biological activity of NF-B plays in widespread human diseases, including cancer; and indeed, blockers of NF-B have already been used successfully to treat otherwise recalcitrant malignancies. As with other functions of NF-B, the suppression of apoptosis involves activation of a program of gene expression. While progress in understanding this program has undoubtedly been made, it remains unclear as to which genes are most critical to this activity of NF-B, and ultimately, by which mechanisms their products inhibit the apoptotic signaling cascade. Recently, an important piece of this puzzle – pertaining to the control of tumor necrosis factor (TNF)-induced apoptosis – has been found, with the demonstration that activation of NF-B shuts down the c-Jun-N-terminal kinase (JNK) cascade1,2,3,4 (Figure 1).