Journal
CELL DEATH AND DIFFERENTIATION
Volume 19, Issue 4, Pages 633-641Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.131
Keywords
PUMA; interleukin-3; post-translational; phosphorylation; degradation; IKK
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Funding
- Sylvia and Charles Viertel Senior Medical Fellowship
- NHMRC of Australia
- Children's Cancer Centre Foundation
- Cancer Council of South Australia
- Leukaemia Research Fund
- University of Adelaide
- University of Melbourne
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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 NF kappa B signaling. The identification and characterization of this novel survival pathway has important implications for IL-3 signaling and hematopoietic cell development. Cell Death and Differentiation (2012) 19, 633-641; doi:10.1038/cdd.2011.131; published online 14 October 2011
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