Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death
- Author(s)
- Sandow, JJ; Jabbour, AM; Condina, MR; Daunt, CP; Stomski, FC; Green, BD; Riffkin, CD; Hoffmann, P; Guthridge, MA; Silke, J; Lopez, AF; Ekert, PG;
- Details
- Publication Year 2012-04,Volume 19,Issue #4,Page 633-641
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- 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 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
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- COLORECTAL-CANCER CELLS; NF-KAPPA-B; APOPTOTIC FUNCTION; BCL-2 PROTEINS; SURVIVAL; BAD; P53; DEPRIVATION; KINASE; BIM
- Research Division(s)
- Cell Signalling And Cell Death
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307976/
- Publisher's Version
- https://doi.org/10.1038/cdd.2011.131
- Terms of Use/Rights Notice
- Copyright © 2012 Macmillan Publishers Limited
Creation Date: 2012-04-01 12:00:00