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Identification of Ipaf, a Human Caspase-1-activating Protein Related to Apaf-1
Open accessAbstract
Procaspase-9 contains an NH2-terminal caspase-associated recruitment domain (CARD), which is essential for direct association with Apaf-1 and activation. Procaspase-1 also contains an NH2-terminal CARD domain, suggesting that its mechanism of activation, like that of procaspase-9, involves association with an Apaf-1-related molecule. Here we describe the identification of a human Apaf-1-related protein, named Ipaf that contains an NH2-terminal CARD domain, a central nucleotide-binding domain, and a COOH-terminal regulatory leucine-rich repeat domain (LRR). Ipaf associates directly and specifically with the CARD domain of procaspase-1 through CARD-CARD interaction. A constitutively active Ipaf lacking its COOH-terminal LRR domain can induce autocatalytic processing and activation of procaspase-1 and caspase-1-dependent apoptosis in transfected cells. Our results suggest that Ipaf is a specific and direct activator of procaspase-1 and could be involved in activation of caspase-1 in response to pro-inflammatory and apoptotic stimuli.
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Cites
Nod1, an Apaf-1-like Activator of Caspase-9 and Nuclear Factor-κB
Inohara, N., Koseki, T., del Peso, L., Hu, Y., Yee, C., Chen, S., Carrio, R., Merino, J., Liu, D., Ni, J., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.21.14560 · Cited by 742
Cited by
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009
Kroemer, G., Galluzzi, L., Vandenabeele, P., Abrams, J., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., El-Deiry, W. S., Golstein, P., Green, D. R., et al. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.150 · Cited by 3,399
Self-citationInflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436
Metadata
- Authors
- Poyet, J.-L., Srinivasula, S. M., Tnani, M., Razmara, M., Fernandes-Alnemri, T., & Alnemri, E. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 276
- Issue
- 30
- Pages
- 28309-28313
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2162295519
- Cited by
- 462
- References
- 1
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Poyet, J.-L., Srinivasula, S. M., Tnani, M., Razmara, M., Fernandes-Alnemri, T., & Alnemri, E. S. (2001). Identification of Ipaf, a Human Caspase-1-activating Protein Related to Apaf-1. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c100250200
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