• Medientyp: E-Artikel
  • Titel: Constitutive NF-κB Activation, Normal Fas-Induced Apoptosis, and Increased Incidence of Lymphoma in Human Herpes Virus 8 K13 Transgenic Mice
  • Beteiligte: Chugh, Priti; Matta, Hittu; Schamus, Sandra; Zachariah, Sunny; Kumar, Arvind; Richardson, James A.; Smith, Alice L.; Chaudhary, Preet M.; Gallo, Robert C.
  • Erschienen: National Academy of Sciences, 2005
  • Erschienen in: Proceedings of the National Academy of Sciences of the United States of America
  • Umfang: 12885-12890
  • Sprache: Englisch
  • ISSN: 0027-8424
  • Schlagwörter: Biological Sciences
  • Zusammenfassung: <p> 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-κB. 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-κB 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-κB activation independent of inhibition of Fas-induced apoptosis. </p>
  • Beschreibung: <p> 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-κB. 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-κB 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-κB activation independent of inhibition of Fas-induced apoptosis. </p>
  • Anmerkungen:
  • Zugangsstatus: Freier Zugang