RIPK1 and Caspase-8 ensure chromosome stability independently of their role in cell death and inflammation

Liccardi, G; Ramos Garcia, L; Tenev, T; Annibaldi, A; Legrand, AJ; Robertson, D; Feltham, R; Anderton, H; Darding, M; Peltzer, N; Dannappel, M; Schunke, H; Fava, LL; Haschka, MD; Glatter, T; Nesvizhskii, A; SCHMIDT, A; Harris, PA; Bertin, J; Gough, PJ; Villunger, A; Silke, J; Pasparakis, M; Bianchi, K; Meier, P

Author(s): Liccardi, G; Ramos Garcia, L; Tenev, T; Annibaldi, A; Legrand, AJ; Robertson, D; Feltham, R; Anderton, H; Darding, M; Peltzer, N; Dannappel, M; Schunke, H; Fava, LL; Haschka, MD; Glatter, T; Nesvizhskii, A; SCHMIDT, A; Harris, PA; Bertin, J; Gough, PJ; Villunger, A; Silke, J; Pasparakis, M; Bianchi, K; Meier, P;
Details: Publication Year 2018-12-28,Volume 73,Issue #3,Page 413-28 e7
Journal Title: Molecular Cell
Publication Type: Journal Article
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.
Publisher: Cell Press
Research Division(s): Cell Signalling And Cell Death
PubMed ID: 30598363
Publisher's Version: https://doi.org/10.1016/j.molcel.2018.11.010
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-01-15 09:07:43

Last Modified: 2019-06-14 11:50:53