Regulation of NF-B by Oncoproteins and Tumor Suppressor Proteins

The transcription factor nuclear factor-κB (NF-κB) has been demonstrated to control cellular proliferation and oncogenesis. Consistent with this, NF-κB activity is stimulated by various mitogenic stimuli and by the action of numerous oncoproteins. This role of NF-κB in controlling oncogenesis is highlighted by observations that many oncoprotein signaling networks lead to the activation of NF-κB and that NF-κB is required for onco-gene-induced cellular transformation (1 ). Furthermore, it has also been demonstrated that various tumor suppressor gene products can function to negatively regulate NF-κB activity. However, evidence has been provided that NF-κB activity is required for the ability of p53 to induce cell death and that NF-κB can regulate p53 gene expression. This review highlights the complex roles that NF-κB subunits play in cellular transformation and analyzes mechanisms of oncoprotein-induced activation and tumor suppressor gene regulation of NF-κB. What is clear is that the role of NF-κB in regulating oncogenic mechanisms is complex, due to stimulus-specific, cell type-specific, or subunit-specific responses.