Reference : SHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
http://hdl.handle.net/2268/35759
SHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic cells by promoting CD95 glycosylation independently of its phosphatase activity
English
Charlier, Edith mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Condé, Claude [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Zhang, Jing [> >]
Deneubourg, Laurence [> >]
Di Valentin, Emmanuel mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Rahmouni, Souad mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Agostinis, Patrizia [> >]
Pang, Poh-Choo [> >]
Haslam, Stuart [> >]
Dell, Anne [> >]
Penninger, Josef [> >]
Erneux, Christophe [> >]
Piette, Jacques mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research >]
Gloire, Geoffrey mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
2010
Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nature Publishing Group
Yes (verified by ORBi)
International
0887-6924
1476-5551
London
United Kingdom
[en] SHIP-1 ; CD95 ; Glycosylation
[en] SHIP-1 functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by PI 3-kinase activity. As a result, SHIP-1 deficiency in mice results in myeloproliferation and B cell lymphoma. On the other hand, SHIP-1 deficient mice have a reduced T cell population, but the underlying mechanisms are unknown. In this work, we hypothesized that SHIP-1 plays anti-apoptotic functions in T cells upon stimulation of the death receptor CD95/APO-1/Fas. Using primary T cells from SHIP-1-/- mice and T leukemic cell lines, we report here that SHIP-1 is a potent inhibitor of CD95-induced death. We observed that a small fraction of the SHIP-1 pool is localized to the endoplasmic reticulum where it promotes CD95 glycosylation. This post-translational modification requires an intact SH2 domain of SHIP-1, but is independent of its phosphatase activity. The glycosylated CD95 fails to oligomerize upon stimulation, resulting in impaired DISC formation and downstream apoptotic cascade. These results uncover an unanticipated inhibitory function for SHIP-1 and emphasize the role of glycosylation in the regulation of CD95 signaling in T cells. This work may also provide a new basis for therapeutic strategies using compounds inducing apoptosis through the CD95 pathway on SHIP-1 negative leukemic T cells.
http://hdl.handle.net/2268/35759

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