Volik, Pavel I Kopeina, Gelina S Zhivotovsky, Boris Zamaraev, Alexey V
Published in
Trends in molecular medicine
The PIDDosome is a multiprotein complex that includes p53-induced protein with a death domain 1 (PIDD1), receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD), and caspase-2, the activation of which is driven by PIDDosome assembly. In addition to the key role of the PIDDosome in the regulation of cell di...
Kim, Ju Youn Wang, Lily Q Sladky, Valentina C Oh, Tae Gyu Liu, Junlai Trinh, Kaitlyn Eichin, Felix Downes, Michael Hosseini, Mojgan Jacotot, Etienne D
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Published in
Cell metabolism
Sterol deficiency triggers SCAP-mediated SREBP activation, whereas hypernutrition together with ER stress activates SREBP1/2 via caspase-2. Whether these pathways interact and how they are selectively activated by different dietary cues are unknown. Here, we reveal regulatory crosstalk between the two pathways that controls the transition from hepa...
Shah, Richa B Kernan, Jennifer L van Hoogstraten, Anya Ando, Kiyohiro Li, Yuanyuan Belcher, Alicia L Mininger, Ivy Bussenault, Andrei M Raman, Renuka Ramanagoudr-Bhojappa, Ramanagouda
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Published in
Developmental cell
Cells counter DNA damage through repair or apoptosis, yet a direct mechanism for this choice has remained elusive. When facing interstrand crosslinks (ICLs), the ICL-repair protein FANCI heterodimerizes with FANCD2 to initiate ICL excision. We found that FANCI alternatively interacts with a pro-apoptotic factor, PIDD1, to enable PIDDosome (PIDD1-RA...
Burigotto, Matteo Fava, Luca L
Published in
Molecular & cellular oncology
The PIDDosome is a Caspase-2-activating platform assembling in response to centrosome amplification or genotoxic stress. We have recently shown that both stimuli depend on ANKRD26 (ankyrin repeat domain-containing protein 26)-mediated localization of PIDD1 (p53-inducible protein with death domain) at the centrosome, demonstrating how this organelle...
Evans, Lauren T Anglen, Taylor Scott, Phillip Lukasik, Kimberly Loncarek, Jadranka Holland, Andrew J
Published in
The EMBO journal
Centriole copy number is tightly maintained by the once-per-cycle duplication of these organelles. Centrioles constitute the core of centrosomes, which organize the microtubule cytoskeleton and form the poles of the mitotic spindle. Centrosome amplification is frequently observed in tumors, where it promotes aneuploidy and contributes to invasive p...
Tsabar, Michael Mock, Caroline S Venkatachalam, Veena Reyes, Jose Karhohs, Kyle W Oliver, Trudy G Regev, Aviv Jambhekar, Ashwini Lahav, Galit
Published in
Cell reports
Cellular responses to stimuli can evolve over time, resulting in distinct early and late phases in response to a single signal. DNA damage induces a complex response that is largely orchestrated by the transcription factor p53, whose dynamics influence whether a damaged cell will arrest and repair the damage or will initiate cell death. How p53 res...
Hiregange, Disha Naick, Hemanth Rao, Basuthkar J
Published in
Cellular signalling
We uncover a novel non-canonical function of ATR kinase in the control of PIDDosome activation, and show that under normal cellular conditions involving no replication stress, ATR kinase controls the phosphorylation of cellular NPM via pChk1 as well as the two phosphatases, PPM1D and PP1β. We show that pNPM triggers the dissociation of NPM from PID...
Sidi, Samuel Bouchier-Hayes, Lisa
Published in
Molecular & cellular oncology
Despite 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 ...
Miles, M A Kitevska-Ilioski, T Hawkins, C J
Published in
International review of cell and molecular biology
Although caspase-2 is a highly conserved protease that has received a lot of research attention, consensus about its roles and the molecular mechanisms that underpin them has been elusive. Recent improvements to our understanding of the activities of caspase-2 have been facilitated by the development and refinement of techniques allowing identifica...
Shah, Richa B Thompson, Ruth Sidi, Samuel
Published in
Molecular & cellular oncology
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 ...
