Regulation of NF-κB by atypical activators and tumour suppressors

Abstract

The RelA(p65) NF-kappaB (nuclear factor kappaB) subunit is typically thought of as being antiapoptotic and tumour-promoting. However, in our laboratory, we have discovered that RelA can inhibit, rather than induce, antiapoptotic gene expression when activated by certain chemotherapeutic drugs, UV light or through the action of the ARF tumour suppressor. These observations explain why RelA can sometimes facilitate rather than inhibit apoptosis and also exhibits tumour-suppressor characteristics in vivo. A better understanding of these processes and an ability to analyse RelA function in tumours could lead to improved cancer diagnosis, choice of therapy and, ultimately, development of new drugs.