Article (Scientific journals)
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
Charlier, Edith; Condé, Claude; Zhang, Jing et al.
2010In Leukemia
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Keywords :
SHIP-1; CD95; Glycosylation
Abstract :
[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.
Disciplines :
Immunology & infectious disease
Author, co-author :
Charlier, Edith ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Condé, Claude ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Zhang, Jing
Deneubourg, Laurence
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Chariot, Alain ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Agostinis, Patrizia
Pang, Poh-Choo
Haslam, Stuart
Dell, Anne
Penninger, Josef
Erneux, Christophe
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research
Gloire, Geoffrey ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
More authors (5 more) Less
Language :
English
Title :
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
Publication date :
2010
Journal title :
Leukemia
ISSN :
0887-6924
eISSN :
1476-5551
Publisher :
Nature Publishing Group, London, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
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