PT  - JOURNAL ARTICLE
AU  - Kang, Tae-Bong
AU  - Ben-Moshe, Tehila
AU  - Varfolomeev, Eugene E.
AU  - Pewzner-Jung, Yael
AU  - Yogev, Nir
AU  - Jurewicz, Anna
AU  - Waisman, Ari
AU  - Brenner, Ori
AU  - Haffner, Rebecca
AU  - Gustafsson, Erika
AU  - Ramakrishnan, Parameswaran
AU  - Lapidot, Tsvee
AU  - Wallach, David
TI  - Caspase-8 Serves Both Apoptotic and Nonapoptotic Roles
AID  - 10.4049/jimmunol.173.5.2976
DP  - 2004 Sep 01
TA  - The Journal of Immunology
PG  - 2976--2984
VI  - 173
IP  - 5
4099  - http://www.jimmunol.org/content/173/5/2976.short
4100  - http://www.jimmunol.org/content/173/5/2976.full
SO  - J. Immunol.2004 Sep 01; 173
AB  - Knockout of caspase-8, a cysteine protease that participates in the signaling for cell death by receptors of the TNF/nerve growth factor family, is lethal to mice in utero. To explore tissue-specific roles of this enzyme, we established its conditional knockout using the Cre/loxP recombination system. Consistent with its role in cell death induction, deletion of caspase-8 in hepatocytes protected them from Fas-induced caspase activation and death. However, application of the conditional knockout approach to investigate the cause of death of caspase-8 knockout embryos revealed that this enzyme also serves cellular functions that are nonapoptotic. Its deletion in endothelial cells resulted in degeneration of the yolk sac vasculature and embryonal death due to circulatory failure. Caspase-8 deletion in bone-marrow cells resulted in arrest of hemopoietic progenitor functioning, and in cells of the myelomonocytic lineage, its deletion led to arrest of differentiation into macrophages and to cell death. Thus, besides participating in cell death induction by receptors of the TNF/nerve growth factor family, caspase-8, apparently independently of these receptors, also mediates nonapoptotic and perhaps even antiapoptotic activities.