2009 Tenovus-Scotland Medal Lecture
Prof Neil Perkins, University of Bristol
Regulation of cancer cell proliferation and survival by NF-kappaB
Aberrantly active NF-κB complexes can contribute to tumorigenesis by regulating genes that promote the growth and survival of cancer cells. However, NF-κB function can vary depending on its cellular context and the nature of the inducing stimulus. Moreover, the pathways that control NF-κB functionality are frequently distinct from the processes that control its ability to translocate to the nucleus of cells. Such pathways include post-translational modifications of the NF-κB subunits as well as interactions with heterologous transcription factors and proteins. For example, NF-κB can act to prevent cell death in response to TNF stimulation but contribute towards apoptosis following treatment with some types of chemotherapeutic drugs, which at least in part can be determined by phosphorylation of the RelA(p65) subunit. NF-κB is also closely integrated with the p53 tumour suppressor protein. Depending on the circumstance, NF-κB can either co-operate with or antagonise p53 activity. We have also investigated NF-κB during the cell cycle and found distinct changes in its activity and promoter occupancy between different phases of the cell cycle. We are interested in learning more about the mechanisms that control the function of NF-κB subunits and how these differ between normal and cancer cells.