Constitutive NF-kappaB activation, normal Fas-induced apoptosis, and increased incidence of lymphoma in human herpes virus 8 K13 transgenic mice.
Proc Natl Acad Sci U S A
; 102(36): 12885-90, 2005 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-16120683
ABSTRACT
Human herpesvirus 8 (HHV-8, also called Kaposi's sarcoma-associated herpes virus) has been linked to Kaposi's sarcoma and primary effusion lymphoma. HHV-8-encoded viral Fas-associated death domain-like IL-1-converting enzyme inhibitory protein (vFLIP) is one of the few viral proteins to be expressed in latently infected cells and plays a key role in the survival and proliferation of primary effusion lymphoma cells. Two main functions have been ascribed to HHV-8 vFLIP, inhibition of caspase 8/Fas-associated death domain-like IL-1-converting enzyme and activation of NF-kappaB. In this article, we demonstrate that vFLIP-expressing transgenic mice lack any of the features seen in mice deficient in caspase 8 or Fas-associated death domain protein and are not resistant to Fas-induced apoptosis. On the other hand, these mice display constitutive activation of classical and alternative NF-kappaB pathways, enhanced response to mitogenic stimuli, and increased incidence of lymphoma. Collectively, our results demonstrate that HHV-8 vFLIP is an oncogenic protein that mimics the signaling activities of caspase 8 during antigen receptor signaling and could contribute to the development of lymphoproliferative disorders via constitutive NF-kappaB activation independent of inhibition of Fas-induced apoptosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
NF-kappa B
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Apoptose
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Receptor fas
/
Linfoma
Tipo de estudo:
Incidence_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article