The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Role of the Kinase MST2 in Suppression of Apoptosis by the Proto-Oncogene Product Raf-1
Abstract
The ablation of the protein kinase Raf-1 renders cells hypersensitive to apoptosis despite normal regulation of extracellular signal–regulated kinases, which suggests that apoptosis protection is mediated by a distinct pathway. We used proteomic analysis of Raf-1 signaling complexes to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20–like kinase (MST2). Raf-1 prevents dimerization and phosphorylation of the activation loop of MST2 independently of its protein kinase activity. Depletion of MST2 from Raf-1 –/– mouse or human cells abrogated sensitivity to apoptosis, whereas overexpression of MST2 induced apoptosis. Conversely, depletion of Raf-1 from Raf-1 +/+ mouse or human cells led to MST2 activation and apoptosis. The concomitant depletion of both Raf-1 and MST2 prevented apoptosis.
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Cites
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The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis
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Tapon, N., Harvey, K. F., Bell, D. W., Wahrer, D. C. R., Schiripo, T. A., Haber, D. A., & Hariharan, I. K. (2002) · Cell · doi:10.1016/s0092-8674(02)00824-3 · Cited by 856
Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway
Udan, R. S., Kango-Singh, M., Nolo, R., Tao, C., & Halder, G. (2003) · Nature Cell Biology · doi:10.1038/ncb1050 · Cited by 747
The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila
Pantalacci, S., Tapon, N., & Léopold, P. (2003) · Nature Cell Biology · doi:10.1038/ncb1051 · Cited by 551
Raf proteins and cancer: B-Raf is identified as a mutational target
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The dark side of Ras: regulation of apoptosis
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Ras Activation of the Raf Kinase: Tyrosine Kinase Recruitment of the MAP Kinase Cascade
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Targeting RAS–ERK signalling in cancer: promises and challenges
Samatar, A. A., & Poulikakos, P. I. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4281 · Cited by 1,163
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
Bahar, M. E., Kim, H. J., & Kim, D. R. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01705-z · Cited by 888
The Salvador–Warts–Hippo pathway — an emerging tumour-suppressor network
Harvey, K., & Tapon, N. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2070 · Cited by 628
Targeting the MAPK pathway in KRAS-driven tumors
Drosten, M., & Barbacid, M. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.013 · Cited by 512
Raf Family Kinases: Old Dogs Have Learned New Tricks
Matallanas, D., Birtwistle, M., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., & Kolch, W. (2011) · Genes & Cancer · doi:10.1177/1947601911407323 · Cited by 386
Self-citation
Metadata
- Authors
- O'Neill, E., Rushworth, L., Baccarini, M., & Kolch, W.
- Venue
- Science
- Published
- 2004-12-24
- Volume
- 306
- Issue
- 5705
- Pages
- 2267-2270
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2047669024
- Cited by
- 317
- References
- 23
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- closed
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- O'Neill, E., Rushworth, L., Baccarini, M., & Kolch, W. (2004). Role of the Kinase MST2 in Suppression of Apoptosis by the Proto-Oncogene Product Raf-1. Science. https://doi.org/10.1126/science.1103233
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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.
