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The inhibitor of de...
The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors
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Djerbi, M (author)
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Screpanti, V (author)
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- Catrina, AI (author)
- Karolinska Institutet
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Bogen, B (author)
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- Biberfeld, P (author)
- Karolinska Institutet
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- Grandien, A (author)
- Karolinska Institutet
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(creator_code:org_t)
- 1999-10-04
- 1999
- English.
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 190:7, s. 1025-1031
- Related links:
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http://jem.rupress.o...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- Death receptor–mediated apoptosis can be modulated by several antiapoptotic proteins, such as the FLICE (FADD [Fas-associated death domain]-like IL-1β–converting enzyme)-inhibitory proteins (FLIPs). The FLIP family includes both cellular and viral members. The Kaposi's sarcoma–associated herpesvirus protein (KSHV)-FLIP is expressed by human herpesvirus 8 (HHV-8), which is associated with malignancies such as Kaposi's sarcoma and certain lymphomas. In this paper, we demonstrate that KSHV-FLIP protects cells from Fas-mediated apoptosis by inhibiting caspase activation and permits clonal growth in the presence of death stimuli in vitro. Furthermore, we show that KSHV-FLIP can act as a tumor progression factor by promoting tumor establishment and growth in vivo. When injected into immunocompetent recipient mouse strains, murine B lymphoma cells (A20) transduced with KSHV-FLIP rapidly develop into aggressive tumors showing a high rate of survival and growth. The tumor-progressive activity of KSHV-FLIP is mediated by prevention of death receptor–induced apoptosis triggered by conventional T cells. Consequently, inhibitors of death receptor signaling can be regarded as a new class of tumor progression factors, and HHV-8–associated tumors may represent naturally occurring examples of the tumorigenic effect of such inhibitors.
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