The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells
Open accessAbstract
The retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses such as the production of type I IFNs. Here we have shown that RIG-I and MDA-5 also initiate a proapoptotic signaling pathway that is independent of type I IFNs. In human melanoma cells, this signaling pathway required the mitochondrial adapter Cardif (also known as IPS-1) and induced the proapoptotic BH3-only proteins Puma and Noxa. RIG-I- and MDA-5-initiated apoptosis required Noxa but was independent of the tumor suppressor p53. Triggering this pathway led to efficient activation of mitochondrial apoptosis, requiring caspase-9 and Apaf-1. Surprisingly, this proapoptotic signaling pathway was also active in nonmalignant cells, but these cells were much less sensitive to apoptosis than melanoma cells. Endogenous Bcl-xL rescued nonmalignant, but not melanoma, cells from RIG-I- and MDA-5-mediated apoptosis. In addition, we confirmed the results of the in vitro studies, demonstrating that RIG-I and MDA-5 ligands both reduced human tumor lung metastasis in immunodeficient NOD/SCID mice. These results identify an IFN-independent antiviral signaling pathway initiated by RIG-I and MDA-5 that activates proapoptotic signaling and, unless blocked by Bcl-xL, results in apoptosis. Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401
RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006) · Science · doi:10.1126/science.1132998 · Cited by 2,210
Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis
Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T., & Tanaka, †. N. (2000) · Science · doi:10.1126/science.288.5468.1053 · Cited by 2,112
Rational siRNA design for RNA interference
Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S., & Khvorova, A. (2004) · Nature Biotechnology · doi:10.1038/nbt936 · Cited by 2,094
Chen, L., Willis, S. N., Wei, A., Smith, B. J., Fletcher, J. I., Hinds, M. G., Colman, P. M., Day, C. L., Adams, J. M., & Huang, D. C. S. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.030 · Cited by 1,816
Immunological aspects of cancer chemotherapy
Zitvogel, L., Apetoh, L., Ghiringhelli, F., & Kroemer, G. (2008) · Nature Reviews Immunology · doi:10.1038/nri2216 · Cited by 1,712
Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Sasaki, S., Imai, K., Shibue, T., Honda, K., et al. (2003) · Nature · doi:10.1038/nature01850 · Cited by 847
5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma
Poeck, H., Besch, R., Maihoefer, C., Renn, M., Tormo, D., Morskaya, S. S., Kirschnek, S., Gaffal, E., Landsberg, J., Hellmuth, J., et al. (2008) · Nature Medicine · doi:10.1038/nm.1887 · Cited by 387
Self-citation
Cited by
Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.056 · Cited by 1,527
Chiba, S., Baghdadi, M., Akiba, H., Yoshiyama, H., Kinoshita, I., Dosaka-Akita, H., Fujioka, Y., Ohba, Y., Gorman, J. V., Colgan, J. D., et al. (2012) · Nature Immunology · doi:10.1038/ni.2376 · Cited by 838
RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8 + T cells
Yatim, N., Jusforgues-Saklani, H., Orozco, S., Schulz, O., Barreira da Silva, R., Reis e Sousa, C., Green, D. R., Oberst, A., & Albert, M. L. (2015) · Science · doi:10.1126/science.aad0395 · Cited by 622
Discriminating self from non-self in nucleic acid sensing
Schlee, M., & Hartmann, G. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.78 · Cited by 593
Self-citationHartmann, G. (2017) · Advances in Immunology · doi:10.1016/bs.ai.2016.11.001 · Cited by 285
Self-citation
Metadata
- Authors
- Besch, R., Poeck, H., Hohenauer, T., Senft, D., Häcker, G., Berking, C., Hornung, V., Endres, S., Ruzicka, T., Rothenfusser, S., & Hartmann, G.
- Venue
- Journal of Clinical Investigation
- Published
- 2009-07-20
- Volume
- 119
- Issue
- 8
- Pages
- 2399-411
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2021140221
- Cited by
- 433
- References
- 11
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells. https://app.cochat.ai/papers/10.1172/jci37155
- The paper
- Besch, R., Poeck, H., Hohenauer, T., Senft, D., Häcker, G., Berking, C., Hornung, V., Endres, S., Ruzicka, T., Rothenfusser, S., & Hartmann, G. (2009). Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci37155
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
