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Nod1, an Apaf-1-like Activator of Caspase-9 and Nuclear Factor-κB
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Ced-4 and Apaf-1 belong to a major class of apoptosis regulators that contain caspase-recruitment (CARD) and nucleotide-binding oligomerization domains. Nod1, a protein with an NH2-terminal CARD-linked to a nucleotide-binding domain and a COOH-terminal segment with multiple leucine-rich repeats, was identified. Nod-1 was found to bind to multiple caspases with long prodomains, but specifically activated caspase-9 and promoted caspase-9-induced apoptosis. As reported for Apaf-1, Nod1 required both the CARD and P-loop for function. Unlike Apaf-1, Nod1 induced activation of nuclear factor-kappa-B (NF-kappaB) and bound RICK, a CARD-containing kinase that also induces NF-kappaB activation. Nod1 mutants inhibited NF-kappaB activity induced by RICK, but not that resulting from tumor necrosis factor-alpha stimulation. Thus, Nod1 is a leucine-rich repeat-containing Apaf-1-like molecule that can regulate both apoptosis and NF-kappaB activation pathways.
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“Notably, Nod1 mRNA and protein levels in the medulla were almost comparable to those in spleen, which is known to express Nod1 at a high level (Figures 1B, S1A, and S1B), as previously reported (Inohara et al., 1999).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Inohara et al., 1999
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Metadata
- Authors
- Inohara, N., Koseki, T., del Peso, L., Hu, Y., Yee, C., Chen, S., Carrio, R., Merino, J., Liu, D., Ni, J., & Núñez, G.
- Affiliations
- University of Michigan (US)
- Human Genome Sciences (United States) (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 274
- Issue
- 21
- Pages
- 14560-14567
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2119502087
- Cited by
- 742
- References
- 55
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 15 · 2023: 9 · 2022: 25 · 2021: 18 · 2020: 19 · 2019: 28 · 2018: 17 · 2017: 24 · 2016: 22 · 2015: 18 · 2014: 35 · 2013: 28 · 2012: 37
- FWCI
- 12.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Michigan (T32GM07863)
- Japan Science and Technology Corporation
- National Institutes of Health (5r01ca064556-10, 5k04ca064421-03)
- National Cancer Institute (K04-CA64421, R01 CA64556)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- NOD1, Apaf-1, caspase-9, apoptosis, NF-κB activation, caspase recruitment domain, nucleotide-binding domain, leucine-rich repeats, cards, P-loop, TNF-α, innate immunity
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Chromosome Mapping, Humans, Molecular Sequence Data, Mutation, Proteins, NF-kappa B, Apoptosis, Caspases, Adaptor Proteins, Signal Transducing, Caspase 9, Nod1 Signaling Adaptor Protein, Apoptotic Protease-Activating Factor 1
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