NF-�ºB signaling pathways play an important role in the regulation of cellular immune\nand stress responses. Aberrant NF-�ºB activity has been implicated in almost all the steps of cancer\ndevelopment and many of the direct and indirect contributions of this transcription factor system\nfor oncogenesis were revealed in the recent years. The indirect contributions affect almost all\nhallmarks and enabling characteristics of cancer, but NF-�ºB can either promote or antagonize these\ntumor-supportive functions, thus prohibiting global NF-�ºB inhibition. The direct effects are due to\nmutations of members of the NF-�ºB system itself. These mutations typically occur in upstream\ncomponents that lead to the activation of NF-�ºB together with further oncogenesis-promoting\nsignaling pathways. In contrast, mutations of the downstream components, such as the DNA-binding\nsubunits, contribute to oncogenic transformation by affecting NF-�ºB-driven transcriptional output\nprograms. Here, we discuss the features of recently identified oncogenic RelA fusion proteins and the\ncharacterization of pathways that are regulating the transcriptional activity of NF-�ºB by regulatory\nphosphorylations. As NF-�ºBâ��s central role in human physiology prohibits its global inhibition,\nthese auxiliary or cell type-specific NF-�ºB regulating pathways are potential therapeutic targets.
Loading....