Nuclear factor-kappa B (NF-κB) activation relies primarily on ubiquitin-mediated degradation of its inhibitor IκB. NF-κB plays an important role in many aspects of tumor development, progression, and therapy. Some types of cancer are characterized by constitutive NF-κB activity, whereas in others such activity is induced following chemotherapy. NF-κB-harboring tumors are generally resistant to chemotherapy and their eradication requires NF-κB inhibition. Here we describe the mechanisms of NF-κB activation in normal and tumor cells, review prevalent notions regarding the factor's contribution to tumorigenicity and discuss present and future options for NF-κB inhibition in cancer. The ubiquitination-mediated activation of NF-κB is intersected by another cancer-associated protein, β-catenin. We, therefore, compare the related activation pathways and discuss the possibility of differential targeting of the involved ubiquitination machinery.
Bibliographical noteFunding Information:
We are grateful to Drs. Eli Pikarsky and A. Mahler for helpful comments on the manuscript. Supported by the Israel Science Foundation funded by the Israel Academy for Sciences and Humanities-Centers of Excellence Program, the German–Israeli Program (DIP), the European Community (5th framework) and the German–Israeli Foundation for Scientific Research (GIF).