Off the beaten pathway: the complex cross talk between Notch and NF-kappaB

The canonical Notch pathway that has been well characterized over the past 25 years is relatively simple compared to the plethora of recently published data suggesting non-canonical signaling mechanisms and cross talk with other pathways. The manner in which other pathways cross talk with Notch signaling appears to be extraordinarily complex and, not surprisingly, context-dependent. While the physiological relevance of many of these interactions remains to be established, there is little doubt that Notch signaling is integrated with numerous other pathways in ways that appear increasingly complex. Among the most intricate cross talks described for Notch is its interaction with the NF-kappaB pathway, another major cell fate regulatory network involved in development, immunity, and cancer. Numerous reports over the last 11 years have described multiple cross talk mechanisms between Notch and NF-kappaB in diverse experimental models. This article will provide a brief overview of the published evidence for Notch-NF-kappaB cross talk, focusing on vertebrate systems.