Direct pro-apoptotic role for NPM1 as a regulator of PIDDosome formation

ABSTRACTDespite being frequently mutated or deregulated in acute myeloid leukemia (AML) and many other cancers, the mechanisms by which nucleophosmin (NPM1) regulates oncogenesis remain elusive. We found that NPM1 plays a direct and conserved role in DNA damage-induced assembly of the PIDDosome complex, the activating platform for caspase-2. This function is carried in the nucleolus and is essential for caspase-2-mediated apoptosis in response to a variety of DNA injuries.