A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis
Open accessAbstract
Significance: Necroptosis is a form of programmed necrotic cell death controlled by receptor-interacting protein kinase 3, RIP3. RIP3 exists in live cells as a latent form in the cytosol and is activated by death-inducing cytokines such as tumor necrosis factor. We report here that RIP3 activation requires Heat Shock Protein 90, HSP90, and its cochaperone protein CDC37. HSP90 inhibitors, currently under investigation in clinical trials for a variety of cancer indications, are capable of inhibiting necroptosis at concentrations below the clinically achieved concentration in patients’ sera. Since the components of the necroptosis pathway are being pursued as potential drug targets for many degenerative diseases, the finding described here revealed that there are already clinical stage molecules available to inhibit necroptosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
RIPK3 activation also depends on physical association with HSP90-containing and CDC37-containing co-chaperone complex.
“RIPK3 activation also depends on its physical association with a HSP90-containing and cell division cycle 37 (CDC37)-containing co-chaperone complex [477].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [477]
Cites
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214 · see citing works
Self-citationHSP90 at the hub of protein homeostasis: emerging mechanistic insights
Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818 · 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
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
Jacobsen, A. V., Lowes, K. N., Tanzer, M. C., Lucet, I. S., Hildebrand, J. M., Petrie, E. J., van Delft, M. F., Liu, Z., Conos, S. A., Zhang, J.-G., et al. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.386 · Cited by 160 · see citing works
Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis
Zhao, X. M., Chen, Z., Zhao, J. B., Zhang, P. P., Pu, Y. F., Jiang, S. H., Hou, J. J., Cui, Y. M., Jia, X. L., & Zhang, S. Q. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.390 · Cited by 135 · see citing works
Molecular mechanisms of necroptosis and relevance for neurodegenerative diseases.
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.12.006 · Cited by 51 · see citing works
Zhao, Q., Yu, X., Zhang, H., Liu, Y., Zhang, X., Wu, X., Xie, Q., Li, M., Ying, H., & Zhang, H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.011 · Cited by 49 · see citing works
- Authors
- Li, D., Xu, T., Cao, Y., Wang, H., Li, L., Chen, S., Wang, X., & Shen, Z.
- Affiliations
- Beijing Normal University (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Shanghai Jiao Tong University (CN)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-04-07
- Volume
- 112
- Issue
- 16
- Pages
- 5017-5022
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4413296
- OpenAlex
- W2133079836
- Cited by
- 167
- References
- 2
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 16 · 2023: 14 · 2022: 16 · 2021: 19 · 2020: 20 · 2019: 9 · 2018: 18 · 2017: 10 · 2016: 22 · 2015: 3
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Ministry of Science and Technology | Department of S and T for Social Development (2010CB835400, 2013CB530805, 2012CB837400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- necroptosis, HSP90, Cdc37, MLKL, RIPK1, TNF signaling, Hsp90 inhibitors, protein folding, systemic inflammatory response syndrome, TNF-α
- MeSH terms
- Animals, Cell Line, Cytosol, Humans, Macrophages, Necrosis, Protein Binding, Protein Kinases, Apoptosis, Cell Cycle Proteins, Chaperonins, HSP90 Heat-Shock Proteins, Mice, Rats, 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
