Manipulation of NK cytotoxicity by the IAP family member Livin.
Eur J Immunol
; 37(12): 3467-76, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-18034418
ABSTRACT
Natural killer (NK) cells are part of the innate immune system, capable of killing tumor and virally infected cells. NK cells induce apoptosis in the target cell by either granule- or receptor-mediated pathways. A set of inhibitory and activation ligands governs NK cell activation. As transformed cells often attempt to evade NK cell killing, up-regulation of a potential anti-apoptotic factor should provide a survival advantage. The inhibitor of apoptosis protein (IAP) family can inhibit apoptosis induced by a variety of stimuli. We have previously described a new IAP family member, termed Livin, which has two splice variants (alpha and beta) with differential anti-apoptotic activities. In this study, we explore the ability of Livin to inhibit NK cell-induced killing. We demonstrate that Livin beta moderately protects against NK cell killing whereas Livin alpha augments killing. We show that Livin beta inhibition in Jurkat cells is apparent upon concomitant activation of an inhibitory signal, suggesting that Livin augments an extrinsic inhibitory signal rather than functioning as an independent inhibitory mechanism. Finally, we demonstrate that detection of both Livin isoforms in melanoma cells correlates with a low killing rate. To date, this is the first evidence that directly demonstrates the ability of IAP to protect against NK cell-induced apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Apoptose
/
Citotoxicidade Imunológica
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas Inibidoras de Apoptose
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2007
Tipo de documento:
Article