CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis.
J Biol Chem
; 278(26): 23915-21, 2003 Jun 27.
Article
en En
| MEDLINE
| ID: mdl-12690108
ABSTRACT
CD47 is a surface receptor that induces either coactivation or apoptosis in lymphocytes, depending on the ligand(s) bound. Interestingly, the apoptotic pathway is independent of caspase activation and cytochrome c release and is accompanied by early mitochondrial dysfunction with suppression of mitochondrial membrane potential (Deltapsim). Using CD47 as bait in a yeast two-hybrid system, we identified the Bcl-2 homology 3 (BH3)-only protein 19 kDa interacting protein-3 (BNIP3), a pro-apoptotic member of the Bcl-2 family, as a novel partner. Interaction between CD47 and the BH3-only protein was confirmed by immunoprecipitation analysis, and CD47-induced apoptosis was inhibited by attenuating BNIP3 expression with antisense oligonucleotides. Finally, we showed that the C-terminal domain of thrombospondin-1 (TSP-1), but not signal-regulatory protein (SIRPalpha1), is the ligand for CD47 involved in inducing cell death. Immunofluorescence analysis of CD47 and BNIP3 revealed a partial colocalization of both molecules under basal conditions. After T cell stimulation via CD47, BNIP3 translocates to the mitochondria to induce apoptosis. These results show that the BH3-dependent apoptotic pathways, previously shown to be activated by intracellular pro-apoptotic events, can also be turned on by surface receptors. This new pathway results in a fast induction of cell death resembling necrosis, which is likely to play an important role in lymphocyte regulation at inflammatory sites and/or in the vicinity of thrombosis.
Search on Google
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Proteínas Portadoras
/
Antígenos CD
/
Proteínas Proto-Oncogénicas
/
Apoptosis
/
Proteínas Supresoras de Tumor
/
Proteínas de la Membrana
Límite:
Humans
Idioma:
En
Año:
2003
Tipo del documento:
Article