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CARP2 deficiency does not alter induction of NFkappaB by TNFα


Ahmed, Afsar U; Moulin, Maryline; Coumailleau, Franck; Wong, W Wei-Lynn; Miasari, Maria; Carter, Holly; Silke, John; Cohen- Tannoudji, Michel; Vince, James E; Vaux, David L (2009). CARP2 deficiency does not alter induction of NFkappaB by TNFα. Current Biology, 19(1):R15-R17.

Abstract

TNFα can activate pathways leading to caspase-8-mediated apoptosis, as well as inflammatory pathways signaled by transcription factors. The adaptor protein RIP1 is a critical component for TNF receptor 1 (TNFR1)-mediated activation of NF-κB, because deletion of the gene encoding RIP1 in mice prevents induction of NF-κB by TNFα and causes severe runting with early postnatal lethality [1]. Recently, it has been proposed that caspase 8 and 10 associated RING protein-2 (CARP2, also named RIFIFYLIN/SAKURA) binds to the TNFR1 complex, leading to ubiquitylation and proteasome-mediated degradation of RIP1, thereby limiting the level of NF-κB activated by TNFα [2]. However, our experiments in mice lacking the Rififylin/Carp2 gene question this conclusion, because levels of RIP1 and induction of NF-κB by TNFα are normal in the absence of CARP2.

TNFα can activate pathways leading to caspase-8-mediated apoptosis, as well as inflammatory pathways signaled by transcription factors. The adaptor protein RIP1 is a critical component for TNF receptor 1 (TNFR1)-mediated activation of NF-κB, because deletion of the gene encoding RIP1 in mice prevents induction of NF-κB by TNFα and causes severe runting with early postnatal lethality [1]. Recently, it has been proposed that caspase 8 and 10 associated RING protein-2 (CARP2, also named RIFIFYLIN/SAKURA) binds to the TNFR1 complex, leading to ubiquitylation and proteasome-mediated degradation of RIP1, thereby limiting the level of NF-κB activated by TNFα [2]. However, our experiments in mice lacking the Rififylin/Carp2 gene question this conclusion, because levels of RIP1 and induction of NF-κB by TNFα are normal in the absence of CARP2.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:15 Jun 2012 15:39
Last Modified:05 Apr 2016 15:33
Publisher:Cell Press; Elsevier
ISSN:0960-9822 (P) 1879-0445 (E)
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1016/j.cub.2008.11.040
PubMed ID:19138581
Permanent URL: http://doi.org/10.5167/uzh-58120

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