Apoptosis is a tightly regulated process responsible for the elimination of dangerous, damaged or unwanted cells from multi-cellular organisms. The Bcl2 family of pro- and anti- apoptotic proteins regulate the mitochondrial or intrinsic cell death pathway. Members of the pro-apoptotic proteins include the BH3-only proteins Puma (p53 up-regulated modifier of apoptosis) and Bim (Bcl-2 interacting mediator of cell death). Pro-apoptotic BH3-only proteins are regulated by transcriptional, post-transcriptional and post-translational levels, in order to control their potent cell death inducing capacity. For example, Puma is transcriptionally up-regulated by the tumour suppressor p53 in response to growth factor withdrawal or DNA damaging agents. We have shown that withdrawal of Interleukin-3 (IL-3) from IL-3 dependent cells resulted in Puma up-regulation resulting in apoptosis in a p53 dependent manner. In contrast, if IL-3 is restored before cells die, Puma protein stability was decreased via a posttranslational mechanism that specifically involved phosphorylation by the IκB kinase, IKK11. Here we aim to determine how IκB kinase is activated by IL-3 and how this results in cell survival. As deregulation of BH3-only proteins contributes to tumour formation, we aim to establish whether there is a functional correlation between the phosphorylation of BH3-only proteins and increased IκB kinase activity in leukaemia.