New insights into the role of nuclear factor-kappaB in cell growth regulation.

The nuclear factor (NF)-kappaB family of eukaryotic transcription factors plays an important role in the regulation of immune response, embryo and cell lineage development, cell apoptosis, cell-cycle progression, inflammation, and oncogenesis. A wide range of stimuli, including cytokines, mitogens, environmental particles, toxic metals, and viral or bacterial products, activate NF-kappaB, mostly through IkappaB kinase (IKK)-dependent phosphorylation and subsequent degradation of its inhibitor, the IkappaB family of proteins. Activated NF-kappaB translocates into the nucleus where it modulates the expression of a variety of genes, including those encoding cytokines, growth factors, acute phase response proteins, cell adhesion molecules, other transcription factors, and several cell apoptosis regulators. During the past few years, tremendous progress has been achieved in our understanding on how intracellular signaling pathways are transmitted in either a linear or a network manner leading to the activation of NF-kappaB and subsequent cell growth control. However, a detailed molecular mechanism of NF-kappaB regulating cell growth has yet to be determined. Elucidation of the relationships between NF-kappaB activation and cell growth will be important in developing new strategies for the treatment of various human diseases, such as chronic autoimmune disorder and cancer.