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|Scopus||Web of Science®||Altmetric|
|Title:||Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death|
|Citation:||Cell Death and Differentiation, 2012; 19(4):633-641|
|Publisher:||Nature Publishing Group|
|JJ Sandow, AM Jabbour, MR Condina, CP Daunt, FC Stomski, BD Green, CD Riffkin, P Hoffmann, MA Guthridge, J Silke, AF Lopez and PG Ekert|
|Abstract:||P53-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.|
|Keywords:||PUMA; interleukin-3; post-translational; phosphorylation; degradation; IKK|
|Rights:||Copyright 2011 Macmillan Publishers Limited|
|Appears in Collections:||IPAS publications|
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