The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors. Export

@article{citeulike:1695601, abstract = {Death receptor-mediated apoptosis can be modulated by several antiapoptotic proteins, such as the FLICE (FADD [Fas-associated death domain]-like IL-1beta-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.}, address = {Department of Immunology, Wenner-Gren Institute, University of Stockholm, S-10691 Stockholm, Sweden.}, author = {Djerbi, M. and Screpanti, V. and Catrina, A. I. and Bogen, B. and Biberfeld, P. and Grandien, A.}, citeulike-article-id = {1695601}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.190.7.1025}, citeulike-linkout-1 = {http://www.jem.org/cgi/content/abstract/190/7/1025}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/10510092}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=10510092}, day = {4}, doi = {10.1084/jem.190.7.1025}, issn = {0022-1007}, journal = {J Exp Med}, keywords = {apoptosisinhibition, kshv, vflip}, month = {October}, number = {7}, pages = {1025--1032}, posted-at = {2007-09-26 01:18:06}, priority = {0}, title = {The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors.}, url = {http://dx.doi.org/10.1084/jem.190.7.1025}, volume = {190}, year = {1999} }

TY - JOUR ID - citeulike:1695601 L3 - citeulike-article-id:1695601 N2 - Death receptor-mediated apoptosis can be modulated by several antiapoptotic proteins, such as the FLICE (FADD [Fas-associated death domain]-like IL-1beta-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. IS - 7 JF - J Exp Med SN - 0022-1007 AD - Department of Immunology, Wenner-Gren Institute, University of Stockholm, S-10691 Stockholm, Sweden. EP - 1032 TI - The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors. VL - 190 SP - 1025 KW - apoptosisinhibition KW - kshv KW - vflip AU - Djerbi, M AU - Screpanti, V AU - Catrina, AI AU - Bogen, B AU - Biberfeld, P AU - Grandien, A PY - 1999/10/04/ UR - http://dx.doi.org/10.1084/jem.190.7.1025 ER -