The role of Jun kinases in apoptosis

The c-Jun amino (N)-terminal kinases along with the ERKs and p38 represent the MAPK family. As we have discussed here, the JNKs modulate the transduction of multiple extracellular signals into intracellular events (Davis, 1994; Robinson & Cobb, 1997). Indeed, since cell proliferation or cell death is typically modulated by extracellular signals, perhaps it is not surprising that the JNKs have been implicated in these processes. In considering the issues raised here, we have found several particularly interesting, including (i) the existence of JNK- independent and dependent apoptosis pathways, which suggests that the JNK pathway may be amenable to therapeutic modulation because apoptosis in every cell-type would not necessarily be altered. (ii) the recent discovery of non-transcription factor JNK substrates, which raises the possibility that this kinase family can act independently of changes in gene expression and (iii) the relative dearth of attention accorded to possible JNK phosphatases, which may yet emerge as important in modulating the JNK pathway. In conclusion, in 1995, the year after the JNKs were identified, 43 scientific papers were published examining the JNKs. In 1998, at least 420 papers were published. Hence, in the four short years since the JNK family was initially identified, scientific investigators have very rapidly demonstrated the importance of this pathway in multiple cellular events. As for the next four years....