| First Author | Ando K | Year | 2017 |
| Journal | J Cell Biol | Volume | 216 |
| Issue | 6 | Pages | 1795-1810 |
| PubMed ID | 28432080 | Mgi Jnum | J:246097 |
| Mgi Id | MGI:5925082 | Doi | 10.1083/jcb.201608095 |
| Citation | Ando K, et al. (2017) NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus. J Cell Biol 216(6):1795-1810 |
| abstractText | The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing, apoptosis, and caspase-2-dependent inhibition of cell growth, demonstrating that the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. Thus we have identified the nucleolus as a novel site for caspase-2 activation and function. |
