Liccardi, Gianmaria, Garcia, Laura Ramos, Tenev, Tencho, Annibaldi, Alessandro ORCID: 0000-0002-0346-4340, Legrand, Arnaud J., Robertson, David, Feltham, Rebecca, Anderton, Holly ORCID: 0000-0003-3913-9686, Darding, Maurice, Peltzer, Nieves ORCID: 0000-0002-4134-5852, Dannappel, Marius, Schunke, Hannah, Fava, Luca L., Haschka, Manuel D., Glatter, Timo, Nesvizhskii, Alexey, Schmidt, Alexander, Harris, Philip A., Bertin, John, Gough, Peter J., Villunger, Andreas, Silke, John ORCID: 0000-0002-7611-5774, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Bianchi, Katiuscia and Meier, Pascal ORCID: 0000-0003-2760-6523 (2019). RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation. Mol. Cell, 73 (3). S. 413 - 436. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

Receptor-interacting protein kinase (RIPK) 1 functions as a key mediator of tissue homeostasis via formation of Caspase-8 activating ripoptosome complexes, positively and negatively regulating apoptosis, necroptosis, and inflammation. Here, we report an unanticipated cell-death-and inflammation- independent function of RIPK1 and Caspase-8, promoting faithful chromosome alignment in mitosis and thereby ensuring genome stability. We find that ripoptosome complexes progressively form as cells enter mitosis, peaking at metaphase and disassembling as cells exit mitosis. Genetic deletion and mitosis-specific inhibition of Ripk1 or Caspase-8 results in chromosome alignment defects independently of MLKL. We found that Polo-like kinase 1 (PLK1) is recruited into mitotic ripoptosomes, where PLK1's activity is controlled via RIPK1-dependent recruitment and Caspase-8-mediated cleavage. A fine balance of ripoptosome assembly is required as deregulated ripoptosome activity modulates PLK1-dependent phosphorylation of downstream effectors, such as BUBR1. Our data suggest that ripoptosome-mediated regulation of PLK1 contributes to faithful chromosome segregation during mitosis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Liccardi, GianmariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia, Laura RamosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tenev, TenchoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Annibaldi, AlessandroUNSPECIFIEDorcid.org/0000-0002-0346-4340UNSPECIFIED
Legrand, Arnaud J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robertson, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feltham, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anderton, HollyUNSPECIFIEDorcid.org/0000-0003-3913-9686UNSPECIFIED
Darding, MauriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peltzer, NievesUNSPECIFIEDorcid.org/0000-0002-4134-5852UNSPECIFIED
Dannappel, MariusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schunke, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fava, Luca L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haschka, Manuel D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glatter, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nesvizhskii, AlexeyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harris, Philip A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertin, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gough, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villunger, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silke, JohnUNSPECIFIEDorcid.org/0000-0002-7611-5774UNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Bianchi, KatiusciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, PascalUNSPECIFIEDorcid.org/0000-0003-2760-6523UNSPECIFIED
URN: urn:nbn:de:hbz:38-156871
DOI: 10.1016/j.molcel.2018.11.010
Journal or Publication Title: Mol. Cell
Volume: 73
Number: 3
Page Range: S. 413 - 436
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4164
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
KINASE; GENE; PHOSPHORYLATION; NECROPTOSIS; HOMEOSTASIS; ACTIVATION; APOPTOSIS; RECEPTOR; MICEMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15687

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