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A Novel Protein That Interacts with the Death Domain of Fas/APO1 Contains a Sequence Motif Related to the Death Domain
Open accessAbstract
Signaling for cell death by Fas/APO1 occurs via a distinct region in its intracellular domain. This region contains a conserved sequence motif, the death domain motif, that is also found in the intracellular domains of the p55 tumor necrosis factor receptor and the low affinity nerve growth factor receptor, as well as in the regulatory domain of the ankyrins. A novel protein that specifically binds to the death domain of Fas/APO1 but not to Fas/APO1 molecules with a loss of function point mutation occurring in lprcg mice was cloned by a two-hybrid screen of a HeLa cells' cDNA library. The cloned protein itself contains a death domain motif, and this region binds to the death domain of Fas/APO1, while the region upstream to the death domain prompts self-association of the protein. Induced expression of the protein results in ligand-independent triggering of cytotoxicity, suggesting that it is involved in cell death induction by Fas/APO1.
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“In the case of FAS and TRAILRs, the cognate ligands—namely, FAS ligand (FASLG; also known as CD95L or APO-1L) and TNF superfamily member 10 (TNFSF10; best known as TRAIL), respectively—stabilize preformed receptor homotrimers to induce a conformational change at their intracellular tails that enables the death domain (DD)-dependent association of the adapter Fas associated via death domain (FADD)”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [277]
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Siegel, R. M., Muppidi, J. R., Roberts, M., Porter, M. B., & Wu, Z. (2003) · Immunologic Research · doi:10.1385/ir:27:2-3:499 · Cited by 35
Koh, P. S., Hughes, G. C., Faulkner, G. R., Keeble, W. W., & Bagby, G. C. (1999) · Experimental Hematology · doi:10.1016/s0301-472x(98)00064-2 · Cited by 35
Tani, E., Kitagawa, H., Ikemoto, H., & Matsumoto, T. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02770-3 · Cited by 35
Metadata
- Authors
- Boldin, M. P., Varfolomeev, E. E., Pancer, Z., Mett, I. L., Camonis, J. H., & Wallach, D.
- Affiliations
- Weizmann Institute of Science (IL)
- Inserm (FR)
- Corresponding author
- Wallach, David
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-04
- Volume
- 270
- Issue
- 14
- Pages
- 7795-7798
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1968328677
- Cited by
- 993
- References
- 27
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 15 · 2018: 17 · 2017: 11 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 15 · 2012: 10
- FWCI
- 34.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- death domain, death receptor signaling, apoptosis, protein-protein interaction, p75 neurotrophin receptor, lpr mice, two-hybrid screen, protein self-association
- MeSH terms
- Amino Acid Sequence, Animals, Antigens, Surface, Carrier Proteins, Cloning, Molecular, HeLa Cells, Humans, Molecular Sequence Data, Proteins, Apoptosis, Sequence Homology, Amino Acid, DNA, Complementary, fas Receptor, Adaptor Proteins, Signal Transducing, Mice, Fas-Associated Death Domain Protein
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