A mitosis-sensing caspase activation platform? New insights into the PIDDosome.
In contrast to the apoptosome and death-inducing signaling complex, the PIDDosome remains an orphan caspase activation platform unassigned to a specific apoptotic pathway. We found that DNA damage-induced PIDDosome formation is blocked by the mitotic checkpoint factor BUBR1 (budding uninhibited by benzimidazole-related 1), via a direct interaction that disrupts the PIDDosome core scaffold. This inhibition occurs at the kinetochore, thus physically connecting the mitotic and apoptotic machineries.
Department of Medicine, Division of Hematology/Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Richa B
RB
Shah
Department of Medicine, Division of Hematology/Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ruth
R
Thompson
Department of Medicine, Division of Hematology/Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Samuel
S
Sidi
Apoptosis; BubR1; DNA damage; PIDD; PIDDosome; RAIDD; caspase-2; kinetochore; mitotic checkpoint