Sandow, J.Jabbour, A.Condina, M.Daunt, C.Stomski, F.Green, B.Riffkin, C.Hoffmann, P.Guthridge, M.Silke, J.Lopez, A.Ekert, P.2011-11-012011-11-012012Cell Death and Differentiation, 2012; 19(4):633-6411350-90471476-5403http://hdl.handle.net/2440/67127P53-upregulated modifier of apoptosis (PUMA), a pro-apoptotic member of the Bcl-2 family, is transcriptionally activated by p53 and is a key effector of p53-dependent apoptosis. We show that PUMA protein is subject to rapid post-translational regulation by phosphorylation at a conserved residue, serine 10, following serum or interleukin-3 (IL-3) stimulation. Serine 10 is not within the Bcl-2 homology (BH3) domain, and PUMA phosphorylated at serine 10 retained the ability to co-immunoprecipitate with antiapoptotic Bcl-2 family members. However, phosphorylated PUMA was targeted for proteasomal degradation indicating that it is less stable than unphosphorylated PUMA. Importantly, we identified IKK1/IKK2/Nemo as the kinase complex that interacts with and phosphorylates PUMA, thereby also demonstrating that IL-3 activates NFκB signaling. The identification and characterization of this novel survival pathway has important implications for IL-3 signaling and hematopoietic cell development.enCopyright 2011 Macmillan Publishers LimitedPUMAinterleukin-3post-translationalphosphorylationdegradationIKKJournal article00201173132011110111462710.1038/cdd.2011.1310003013741000092-s2.0-8485815653525501Lopez, A. [0000-0001-7430-0135]