Caspase-8 serves both apoptotic and nonapoptotic roles
(2004) In Journal of Immunology 173(5). p.2976-2984- Abstract
- 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... (More)
- 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. (Less)
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https://lup.lub.lu.se/record/268484
- author
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 173
- issue
- 5
- pages
- 2976 - 2984
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000223529800018
- pmid:15322156
- scopus:4344560197
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000)
- id
- a6499ec6-fa53-4f85-bea9-47cd1a2e9c93 (old id 268484)
- alternative location
- http://www.jimmunol.org/cgi/content/abstract/173/5/2976
- date added to LUP
- 2016-04-01 16:06:54
- date last changed
- 2022-04-22 19:42:32
@article{a6499ec6-fa53-4f85-bea9-47cd1a2e9c93, abstract = {{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.}}, author = {{Kang, TB and Ben-Moshe, T and Varfolomeev, EE and Pewzner-Jung, Y and Yogev, N and Jurewicz, A and Waisman, A and Brenner, O and Haffner, R and Gustafsson, Erika and Ramakrishnan, P and Lapidot, T and Wallach, D}}, issn = {{1550-6606}}, language = {{eng}}, number = {{5}}, pages = {{2976--2984}}, publisher = {{American Association of Immunologists}}, series = {{Journal of Immunology}}, title = {{Caspase-8 serves both apoptotic and nonapoptotic roles}}, url = {{http://www.jimmunol.org/cgi/content/abstract/173/5/2976}}, volume = {{173}}, year = {{2004}}, }