Journal article
LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis
N Peltzer, M Darding, A Montinaro, P Draber, H Draberova, S Kupka, E Rieser, A Fisher, C Hutchinson, L Taraborrelli, T Hartwig, E Lafont, TL Haas, Y Shimizu, C Böiers, A Sarr, J Rickard, S Alvarez-Diaz, MT Ashworth, A Beal Show all
Nature | NATURE PUBLISHING GROUP | Published : 2018
Abstract
The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death 2-8 . In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype 9-11 . Here we show, by creating HOIL-1-deficient mice, that HOIL-1 is as essential for LUBAC function as HOIP, albei..
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Awarded by European Commission
Funding Acknowledgements
V. Dixit and K. Newton provided Ripk3<SUP>-/-</SUP> mice, S. Hedrick and R. Hakem provided Casp8<SUP>fl/fl</SUP> mice; H. Anderton and U. Nachbur helped with Sharpin<SUP>cpdm</SUP> analysis; P. Levy and staff and L. Lawrence provided technical and histology services. A. Leister and J. Marinis advised on GSK'457A. T. Marafioti and A. Akarsa helped with phosphorylated MLKL detection. A. Annibaldi provided scientific advice and helpful discussions. B.J. Ferguson provided reagents and advice. The flow cytometry, microscopy and imaging core facilities are supported by Cancer Research UK through the CRUK-UCL Centre (515818) and a Cancer Immunotherapy Accelerator award (CITA, 525877). This work was funded by a Wellcome Trust Senior Investigator Award (096831/Z/11/Z), an ERC Advanced grant (294880) and a Cancer Research UK programme grant (A17341) awarded to H.W., NHMRC grants awarded to P.B., A.St., J. S. and H.W. (602516, 1037321, 1043414, 1080321, 1105209, 461221, 1042629, 1057905), the Leukemia and Lymphoma Society (Specialised Center of Research grant 7015) and a postdoctoral fellowship awarded to N.P. by the Swiss National Science Foundation (P300P3_158509).