Pathobiology in Focus
Laboratory Investigation (2008) 88, 11–17; doi:10.1038/labinvest.3700700; published online 3 December 2007
Off the beaten pathway: the complex cross talk between Notch and NF-
B
Clodia Osipo1,2, Todd E Golde3, Barbara A Osborne4 and Lucio A Miele1,2,5
- 1Breast Cancer Program, Cardinal Bernadin Cancer Center, Loyola University Medical Center, Maywood, IL, USA
- 2Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
- 3Department of Neurology, The Mayo Clinic, Jacksonville, FL, USA
- 4Department of Veterinary and Animal Sciences, The University of Massachusetts, Amherst, MA, USA
- 5Departments of Pharmacology and Experimental Therapeutics, Loyola University Medical Center, Maywood, IL, USA
Correspondence: Dr L Miele, MD, PhD, Breast Cancer Basic Program, Cardinal Bernadin Cancer Center, Loyola University Medical Center, 2160 S First Avenue, Maywood, IL 60513, USA. E-mail: lmiele@lumc.edu
Received 16 September 2007; Revised 18 October 2007; Accepted 19 October 2007; Published online 3 December 2007.
Abstract
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-
B 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-
B in diverse experimental models. This article will provide a brief overview of the published evidence for Notch–NF-
B cross talk, focusing on vertebrate systems.
Keywords:
Notch signaling, NF-
B cross talk, non-canonical signaling, IKK kinases
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