| First Author | Sandow JJ | Year | 2012 |
| Journal | Cell Death Differ | Volume | 19 |
| Issue | 4 | Pages | 633-41 |
| PubMed ID | 21997190 | Mgi Jnum | J:203077 |
| Mgi Id | MGI:5524190 | Doi | 10.1038/cdd.2011.131 |
| Citation | Sandow JJ, et al. (2012) Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death. Cell Death Differ 19(4):633-41 |
| abstractText | 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 NFkappaB signaling. The identification and characterization of this novel survival pathway has important implications for IL-3 signaling and hematopoietic cell development. |
