RIP mediates tumor necrosis factor receptor 1 activation of NF‐kappaB but not Fas/APO‐1‐initiated apoptosis.
Open accessAbstract
The CD95 (Fas/APO-1) and tumor necrosis factor (TNF) receptor pathways share many similarities, including a common reliance on proteins containing 'death domains' for elements of the membrane-proximal signal relay. We have created mutant cell lines that are unable to activate NF-kappaB in response to TNF. One of the mutant lines lacks RIP, a 74 kDa Ser/Thr kinase originally identified by its ability to associate with Fas/APO-1 and induce cell death. Reconstitution of the line with RIP restores responsiveness to TNF. The RIP-deficient cell line is susceptible to apoptosis initiated by anti-CD95 antibodies. An analysis of cells reconstituted with mutant forms of RIP reveals similarities between the action of RIP and FADD/MORT-1, a Fas-associated death domain protein.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
At least in some settings, this reflects major role of RIPK1 in NF-κB activation.
“At least in some settings, this reflects the major role of RIPK1 in NF-κB activation [505–507].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [506]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Vermes, I., Haanen, C., Steffens-Nakken, H. M., & Reutellingsperger, C. (1995) · Journal of Immunological Methods · doi:10.1016/0022-1759(95)00072-i · Cited by 5,437 · see citing works
Current protocols in molecular biology
(1988) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(88)90131-4 · Cited by 4,234 · see citing works
Martin, S. J., Reutelingsperger, C. P., McGahon, A. J., Rader, J. A., van Schie, R. C., LaFace, D. M., & Green, D. R. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.5.1545 · Cited by 2,824 · see citing works
Chinnaiyan, A. M., O'Rourke, K., Tewari, M., & Dixit, V. M. (1995) · Cell · doi:10.1016/0092-8674(95)90071-3 · Cited by 2,431 · see citing works
Kischkel, F. C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P. H., & Peter, M. E. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00245.x · Cited by 2,181 · see citing works
The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation
Hsu, H., Xiong, J., & Goeddel, D. V. (1995) · Cell · doi:10.1016/0092-8674(95)90070-5 · Cited by 2,024 · see citing works
Hsu, H., Shu, H., Pan, M., & Goeddel, D. V. (1996) · Cell · doi:10.1016/s0092-8674(00)80984-8 · Cited by 1,998 · see citing works
The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death
Smith, C. A., Farrah, T., & Goodwin, R. G. (1994) · Cell · doi:10.1016/0092-8674(94)90372-7 · Cited by 1,909 · see citing works
Current protocols in immunology
Nezlin, R. S. (1992) · Molecular Immunology · doi:10.1016/0161-5890(92)90114-d · Cited by 1,413 · see citing works
A novel domain within the 55 kd TNF receptor signals cell death
Tartaglia, L. A., Ayres, T. M., Wong, G. H., & Goeddel, D. V. (1993) · Cell · doi:10.1016/0092-8674(93)90464-2 · Cited by 1,290 · see citing works
TNF-Dependent Recruitment of the Protein Kinase RIP to the TNF Receptor-1 Signaling Complex
Hsu, H., Huang, J., Shu, H.-B., Baichwal, V., & Goeddel, D. V. (1996) · Immunity · doi:10.1016/s1074-7613(00)80252-6 · Cited by 1,182 · see citing works
Induction of apoptosis in mature T cells by tumour necrosis factor
Zheng, L., Fisher, G. H., Miller, R. E., Peschon, J. J., Lynch, D. H., & Lenardo, M. J. (1995) · Nature · doi:10.1038/377348a0 · Cited by 1,116 · see citing works
Rothe, M., Wong, S. C., Henzel, W. J., & Goeddel, D. V. (1994) · Cell · doi:10.1016/0092-8674(94)90532-0 · Cited by 1,054 · see citing works
TRAF2-Mediated Activation of NF-κB by TNF Receptor 2 and CD40
Rothe, M., Sarma, V. J., Dixit, V. M., & Goeddel, D. V. (1995) · Science · doi:10.1126/science.7544915 · Cited by 1,050 · see citing works
Rothe, M., Pan, M.-G., Henzel, W. J., Ayres, T. M., & V. Goeddel, D. (1995) · Cell · doi:10.1016/0092-8674(95)90149-3 · Cited by 1,030 · see citing works
Boldin, M. P., Varfolomeev, E. E., Pancer, Z., Mett, I. L., Camonis, J. H., & Wallach, D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.14.7795 · Cited by 993 · see citing works
Mosialos, G., Birkenbacht, M., Yalamanchill, R., Arsdale, T. V., Ware, C. F., & Kleff, E. (1995) · Cell · doi:10.1016/0092-8674(95)90489-1 · Cited by 980 · see citing works
Stanger, B. Z., Leder, P., Lee, T.-H., Kim, E., & Seed, B. (1995) · Cell · doi:10.1016/0092-8674(95)90072-1 · Cited by 969 · see citing works
Self-citationMolecular cloning and expression of the human 55 kd tumor necrosis factor receptor
Loetscher, H., Pan, Y. E., Lahm, H., Gentz, R., Brockhaus, M., Tabuchi, H., & Lesslauer, W. (1990) · Cell · doi:10.1016/0092-8674(90)90815-v · Cited by 897 · see citing works
Chinnaiyan, A. M., Tepper, C. G., Seldin, M. F., O’Rourke, K. M., Kischkel, F. C., Hellbardt, S., Krammer, P. H., Peter, M. E., & Dixit, V. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.9.4961 · Cited by 767 · see citing works
A rapid and simple method for the isolation of apoptotic DNA fragments
i, M. H., Lorenz, H.-M., Voll, R. E., Griinke, M., Woith, W., & Kalden, J. R. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.24.5506 · Cited by 652 · see citing works
Involvement of CRAF1, a relative of TRAF, in CD40 signaling
Cheng, G., Cohen, A. C., Ye, Z.-S., Hong, D., Lederman, S. M., & Baltimore, D. (1995) · Science · doi:10.1126/science.7533327 · Cited by 449 · see citing works
Boldin, M., Mett, I. L., Varfolomeev, E. E., Chumakov, I., Shemer‐Avni, Y., Camonis, J., & Wallach, D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.1.387 · Cited by 386 · see citing works
Cross-linking CD40 on B cells rapidly activates nuclear factor- kappa B.
Berberich, I., Shu, G. L., & Clark, E. A. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.10.4357 · Cited by 358 · see citing works
A novel RING finger protein interacts with the cytoplasmic domain of CD40.
Hu, H., O’Rourke, K. M., Boguski, M. S., & Dixit, V. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43772-6 · Cited by 341 · see citing works
Kohno, T., Brewer, M. T., Baker, S. L., Schwartz, P. E., King, M. W., Hale, K. K., Squires, C. H., Thompson, R. C., & Vannice, J. L. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8331 · Cited by 289 · see citing works
TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB activation.Preprint
Cheng, G., & Baltimore, D. (1996) · Genes & Development · doi:10.1101/gad.10.8.963 · Cited by 288 · see citing works
Schattner, E. J., Elkon, K. B., Yoo, D., et al. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.5.1557 · Cited by 284 · see citing works
McKendry, R., John, J., Flavell, D. M., Müller, M. M., Kerr, I. M., & Stark, G. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.24.11455 · Cited by 262 · see citing works
Sato, T., Irie, S., & Reed, J. C. (1995) · FEBS Letters · doi:10.1016/0014-5793(94)01406-q · Cited by 177 · see citing works
Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions.
Clement, M., & Stamenkovic, I. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.2.557 · Cited by 142 · see citing works
Ting, A. T., Karnitz, L. M., Schoon, R. A., Abraham, R. T., & Leibson, P. J. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.6.1751 · Cited by 133 · see citing works
Self-citationVarfolomeev, E. E., Boldin, M., Goncharov, T. M., & Wallach, D. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.1271 · Cited by 132 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Death Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866 · see citing works
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842 · see citing works
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435 · see citing works
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
TAK1 is a ubiquitin-dependent kinase of MKK and IKK
Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J.-I., & Chen, Z. J. (2001) · Nature · doi:10.1038/35085597 · Cited by 2,125 · see citing works
Identification of RIP1 kinase as a specific cellular target of necrostatins
Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.83 · Cited by 2,059 · see citing works
NF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693 · see citing works
Tili, E., Michaille, J.-J., Cimino, A., Costinean, S., Dumitru, C. D., Adair, B., Fabbri, M., Alder, H., Liu, C. G., Calin, G. A., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5082 · Cited by 1,304 · see citing works
The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal
Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B. Z., & Leder, P. (1998) · Immunity · doi:10.1016/s1074-7613(00)80535-x · Cited by 1,102 · see citing works
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016 · see citing works
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998 · see citing works
Hitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J., & Yuan, J. (2008) · Cell · doi:10.1016/j.cell.2008.10.044 · Cited by 989 · see citing works
A Domain in TNF Receptors That Mediates Ligand-Independent Receptor Assembly and Signaling
Chan, F. K.-M., Chun, H. J., Zheng, L., Siegel, R. M., Bui, K. L., & Lenardo, M. J. (2000) · Science · doi:10.1126/science.288.5475.2351 · Cited by 856 · see citing works
Festjens, N., Vanden Berghe, T., & Vandenabeele, P. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.06.014 · Cited by 710 · see citing works
Tada, K., Okazaki, T., Sakon, S., Kobarai, T., Kurosawa, K., Yamaoka, S., Hashimoto, H., Mak, T. W., Yagita, H., Okumura, K., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104837200 · Cited by 306 · see citing works
Beck, I. M. E., Vanden Berghe, W., Vermeulen, L., Yamamoto, K. R., Haegeman, G., & De Bosscher, K. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0013 · Cited by 298 · see citing works
Ubiquitination of RIP Is Required for Tumor Necrosis Factor α-induced NF-κB Activation
Li, H., Kobayashi, M., Blonska, M., You, Y., & Lin, X. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600620200 · Cited by 277 · see citing works
NEMO and RIP1 Control Cell Fate in Response to Extensive DNA Damage via TNF-α Feedforward Signaling
Biton, S., & Ashkenazi, A. (2011) · Cell · doi:10.1016/j.cell.2011.02.023 · Cited by 262 · see citing works
Heyninck, K., & Beyaert, R. (1999) · FEBS Letters · doi:10.1016/s0014-5793(98)01645-7 · Cited by 169 · see citing works
Lu, J. V., Weist, B. M., van Raam, B. J., Marro, B. S., Nguyen, L. V., Srinivas, P., Bell, B. D., Luhrs, K. A., Lane, T. E., Salvesen, G. S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102779108 · Cited by 122 · see citing works
Molecular basis of the cell specificity of cytokine action
Ishihara, K., & Hirano, T. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00321-x · Cited by 122 · see citing works
RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice
Liu, Y., Fan, C., Zhang, Y., Yu, X., Wu, X., Zhang, X., Zhao, Q., Zhang, H., Xie, Q., Li, M., et al. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.78 · Cited by 42 · see citing works
Apoptosis in primary lymphoid organs with aging
Sainz, R. M., Mayo, J. C., Reiter, R. J., Tan, D. X., & Rodriguez, C. (2003) · Microscopy Research and Technique · doi:10.1002/jemt.10414 · Cited by 32 · see citing works
Rosebeck, S., Rehman, A. O., Apel, I. J., Kohrt, D., Appert, A., O'Donnell, M. A., Ting, A. T., Du, M.-Q., Baens, M., Lucas, P. C., et al. (2014) · Oncogene · doi:10.1038/onc.2013.195 · Cited by 27 · see citing works
Self-citation
- Authors
- Ting, A. T., Pimentel‐Muiños, F. X., & Seed, B.
- Affiliations
- Massachusetts General Hospital (US)
- Venue
- The EMBO Journal
- Published
- 1996-11-01
- Volume
- 15
- Issue
- 22
- Pages
- 6189-6196
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC452440
- OpenAlex
- W135294775
- Cited by
- 550
- References
- 33
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 8 · 2019: 12 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 14 · 2014: 21 · 2013: 18 · 2012: 21
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- Massachusetts General Hospital
- National Institutes of Health (5r01dk043031-10)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 43031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- receptor-interacting protein, RIP, tumor necrosis factor receptor 1, NF-κB activation, Fas/APO-1, Fas, apoptosis, death domain, TNF signaling, Ser/Thr kinase
- MeSH terms
- Animals, Cells, Cultured, DNA, Flow Cytometry, Gene Expression Regulation, Phosphatidylserines, Phosphoserine, Phosphothreonine, Proteins, Transfection, Immunoblotting, Blotting, Western, Mutagenesis, NF-kappa B, Apoptosis, Genes, Reporter, Receptors, Tumor Necrosis Factor, fas Receptor, Mice, Receptor-Interacting Protein Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
